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Object Although glucocorticoids are essential for health, several studies have shown that glucocorticoids replacement in Addison's disease might be involved in anthropometric and metabolic impairment, with increased cardiovascular risk, namely if conventional doses are used. As the effects of glucocorticoids are mediated by the glucocorticoid receptor, encoded by NR3C1 gene, different polymorphisms in the NR3C1 gene have been linked to altered glucocorticoid sensitivity in general population as well as in patients with obesity or metabolic syndrome. Design We investigated the impact of glucocorticoid receptor gene polymorphisms, including the BclI, N363S and ER22/23EK variants, on anthropometric parameters (BMI and waist circumference), metabolic profile (HOMA, OGTT and serum lipids) and ACTH levels in 50 patients with Addison's disease (34 women and 16 men, age 20–82 year) under glucocorticoids replacement. Results Neither N363S nor ER22/23EK variants were significantly associated with anthropometric, metabolic or hormonal parameters, while patients carrying the homozygous BclI polymorphism GG (n = 4) showed higher (P

Aims Several studies confirmed the growing rate of Type 1 diabetes mellitus in childhood coinciding with increasing diagnosis of viral infections. A study investigating the incidence of Type 1 diabetes during 1996-1997 showed a higher notification of viral infections in the Pavia District. The aim was to confirm these results. Methods This study evaluated the relationship between new cases of Type 1 diabetes and those of measles, mumps and rubella in 1996-2001, analysing data of newly-diagnosed Type 1 diabetes children, aged 0-14 years and enrolled into the RIDI (Italian Insulin-dependent Diabetes Registry) during the same years. Measles, rubella and mumps rates were calculated using as denominator the estimated 'population at risk', represented by the number of 0- to 14 year-old subjects who did not undergo the MMR (measles, mumps and rubella) vaccination. In order to investigate the association between Type 1 diabetes incidence and measles, rubella and mumps respectively, Spearman's rank correlation was used. Results The analysis of the whole Registries data did not at first show any statistical significance between age-standardized Type 1 diabetes incidence density and estimated rates of measles, mumps and rubella notifications. Excluding data from Sardinia Registry, a significant association was observed between Type 1 diabetes incidence and mumps (P = 0.034) and rubella (P = 0.014), respectively, while there was no statistical significance between the incidence of measles cases and diabetes rates (P = 0.269). Conclusions According to our findings, mumps and rubella viral infections are associated with the onset of Type 1 diabetes. The statistical significance observed after exclusion of the Sardinian data suggests that other environmental factors may operate over populations with different genetic susceptibility.

We describe an attractive cloning system for the seed-specific expression of recombinant proteins using three non-food/feed crops. A vector designed for direct subcloning by Gateway® recombination was developed and tested in Arabidopsis, tobacco and petunia plants for the production of a chimeric form (GAD67/65) of the 65 kDa isoform of glutamic acid decarboxylase (GAD65). GAD65 is one of the major human autoantigens involved in type 1 diabetes (T1D). The murine anti-inflammatory cytokine interleukin-10 (IL-10) was expressed with the described system in Arabidopsis and tobacco, whereas proinsulin, another T1D major autoantigen, was expressed in Arabidopsis. The cost-effective production of these proteins in plants could allow the development of T1D prevention strategies based on the induction of immunological tolerance. The best yields were achieved in Arabidopsis seeds, where GAD67/65 reached 7.7% of total soluble protein (TSP), the highest levels ever reported for this protein in plants. IL-10 and proinsulin reached 0.70% and 0.007% of TSP, respectively, consistent with levels previously reported in other plants or tissues. This versatile cloning vector could be suitable for the high-throughput evaluation of expression levels and stability of many valuable and difficult to produce proteins.

The 65-kDa isoform of glutamic acid decarboxylase (GAD65) is the major autoantigen implicated in the development of type 1 diabetes mellitus (T1DM). The bulk manufacture of GAD65 is a potential issue in the fight against T1DM but current production platforms are expensive. We show that a catalytically inactive form of GAD65 (GAD65mut) accumulates at up to 2.2% total soluble protein in transgenic tobacco leaves, which is more than 10-fold the levels achieved with active GAD65, yet the protein retains the immunogenic properties required to treat T1DM. This higher yield was found to be a result of a higher rate of protein synthesis and not transcript availability or protein stability. We found that targeting GAD65 to the endoplasmic reticulum, a strategy that increases the accumulation of many recombinant proteins expressed in plants, did not improve production of GAD65mut. The production of a catalytically inactive autoantigen that retains its immunogenic properties could be a useful strategy to provide high-quality therapeutic protein for treatment of autoimmune T1DM.

This paper describes a new application of holographic radar for non-destructive testing applied to cultural heritage items. A holographic radar, called RASCAN, operates in continuous wave multi-frequency mode at 4 GHz range and produces images with high in-plane resolution (about 2 cm). Marble items and other stones have been investigated to validate the method to search for subtle cracks, moisture or to unveil details of structures at shallow depth (up to 2 wavelengths). Other important materials are aged wood items that are investigated for tunnels made by insects. Then the holographic radar imaging has been experimentally compared with infrared thermography to understand the advantages and disadvantages of these methods and to derive indications for solving the problem common in all geophysics of inherent non-uniqueness.

This paper explores the application of the RASCAN holographic radar for non-destructive subsurface imaging of works of art and architecture. This radar provides high-resolution plan-view images of the shallow subsurface in dielectric materials. The radar is particularly sensitive to small metallic targets, but also to variations in moisture content. Originally developed for detection of hidden bugging devices, sounding of building construction details, and detection of landmines, here the utility of the RASCAN radar for art and architectural preservation studies is demonstrated by several bench-top experiments on stone and wood items with different subsurface defects and features, as well as actual field tests on a decorative marble medallion in the floor of the Temple of San Biagio in Montepulciano, Italy, and Frescoes in the Church of San Rocco in Cornaredo, Italy. Historical research indicates that the medallion in San Biagio was laid circa 1590 during the funeral ceremony of a Prelatio of the family Casata Cervini. The actual burial place of the Prelatio is not recorded, but a radar scan of the medallion, and follow-up scans of a bench-top model suggest the possibility of a cavity that could contain remains or relics. In San Rocco, small delaminations were detected behind the frescos. Copyright © 2009 John Wiley & Sons, Ltd.

Massi-Benedetti, F., Marini, A., Caccamo, M. L. and Falorni, A. (Paediatric Clinic of the University of Perugia and the Service of Neonatal Pathology of the University of -Milan, Italy). Blood glucose and plasma insulin and glucagon response during intravenous glucose tolerance test in newborn infants affected by erythroblastosis foetalis. Acta Paediatr Scand, 64:113, 1975.–Intravenous glucose injection (1 g/kg b.w.) was performed in eight newborn infants affected by erythroblastosis foetalis (IEF) and in seven controls during the first day of life in order to study insulin and glucagon response. The IEF infants were affected by mild or moderate hemolytic disease and their blood glucose values and plasma insulin concentrations before and throughout the test did not differ significantly from those of the controls. After the glucose injection the plasma glucagon concentrations showed great variations in both groups. The control infants did not show any significant changes; in the IEF infants, significant decreases were seen at 3 and 20 min of the test. These data seem to indicate that the alpha-cell sensitivity to glucose is greater in IEF than in normal infants and is not dependent on the development of the glucose-mediated insulin release mechanism.

Aim To determine the influence of Type 1 diabetes mellitus on circulating adipocytokines in children. Methods The circulating concentrations of leptin, adiponectin, resistin and tumour necrosis factor (TNF)-α were measured in 91 children, aged 11.1 ± 2.7 years, with Type 1 diabetes mellitus (T1DM). Ninety-one healthy children were selected as control subjects. Results Body mass index-adjusted leptin concentrations were higher in the pubertal diabetic children compared with the control children. There was a significant positive correlation between leptin and daily insulin dose in the diabetic group. Circulating adiponectin concentrations were higher in the prepubertal diabetic children and were positively associated with HbA1c. Resistin concentrations were lower in the prepubertal non-diabetic subjects compared with the pubertal non-diabetic children, whose values were higher than those of the diabetic children. TNF-α concentrations were similar in non-diabetic and diabetic children. Conclusions Circulating concentrations of adipocytokines are abnormal in Type 1 diabetic children, although the direction of change differs by cytokine. Pubertal development, in addition to insulin treatment and glycaemic control, also influences the concentrations.

Latent autoimmune diabetes in adults (LADA) is identified by the presence of GAD65 autoantibodies in diabetic patients who do not require insulin treatment for at least six months after the diagnosis. Previous studies have shown that the risk for LADA, similarly to type 1 diabetes mellitus (T1DM), is increased in subjects carrying the HLA-DRB1*03-DQA1*0501-DQB1*0201 and/or HLA-DRB1*04-DQA1*0301-DQB1*0302 haplotypes. In the present study, we investigated the association between LADA and the CTLA-4 A/G polymorphism, another gene polymorphism associated with T1DM and other autoimmune diseases. The heterozygous A/G genotype was significantly more frequent among 80 LADA (69%) than among 85 healthy subjects of similar age and geographical provenience (47%) (OR = 2.47, corrected P= 0.023). Conversely, the homozygous A/A genotype was significantly less frequent in LADA subjects than in healthy controls (26% vs. 47%, OR = 0.4, corrected P= 0.028). The results of our study show that LADA is positively associated with the CTLA-4 A/G genotype, similarly to T1DM, thus providing further supporting evidence of the autoimmune origin of this form of diabetes mellitus of the adult.

Slowly progressive insulin-dependent diabetes mellitus (IDDM), like classical IDDM, is also associated with genetic markers. HLA-DR3 but not DR4 is associated with latent autoimmune diabetes in adults (LADA). In GAD65 antibody-positive Finnish LADA patients, DQB1*0302 is positively associated with the disease. Alleles of the MHC class I chain-related A (MICA) gene located centromeric to the HLA-B gene is associated with LADA. Allele 5.1 of MICA was associated with both LADA and adult-onset Italian IDDM patients when compared to controls. This finding was also observed in Indian and Latvian patients with LADA. These findings suggest that certain genetic markers distinguish LADA better.

Summary Objective To study the circulating levels of two gut-derived peptides in children with type 1 (insulin-dependent) diabetes mellitus (IDDM). Research Design and Methods Plasma levels of ghrelin, both total ghrelin (TG) and the acylated form (AG), and galanin and their relationships with insulin dosage, metabolic control, IGFBP-1, body mass and pubertal development were evaluated in 91 children, aged 11·1 ± 2·7 years, affected by IDDM and treated with insulin. Ninety-one healthy children were selected as controls. Results Body mass index (BMI)-adjusted levels of both forms of ghrelin were reduced in IDDM compared with healthy subjects, with greater values in prepubertal than pubertal IDDM subjects. A negative association was found between AG and fasting insulin serum levels and insulin resistance [measured by using the homeostasis model assessment of insulin resistance (HOMA IR)] among the healthy children. IDDM children showed a negative association of their plasma ghrelin (both acylated and total) with daily insulin dosage, and the three adiposity indices (BMI, skinfold thickness and percentage fat mass). IGFBP-1 levels were higher among the IDDM children without any association with ghrelin serum values. BMI-adjusted plasma levels of galanin were higher among IDDM compared to healthy subjects, irrespective of sex or pubertal development. Greater values for galanin were found among pubertal than prepubertal subjects in both groups without any significant differences between the genders. A positive association was found between galanin and BMI in both groups and between galanin and haemoglobin A1c (HbA1c) among the IDDM children. No relationship existed between either galanin and fasting serum insulin among the healthy subjects or galanin and both insulin dosage or duration of treatment among the IDDM subjects. Conclusions The associations found between both ghrelin and galanin with adiposity indices could be considered as an indirect signal of involvement of the two peptides in the development of the nutritional status of the IDDM adolescents. The reduction in both forms of ghrelin could be involved in the development of the body mass increase of IDDM subjects with opposite effects, either influencing insulin sensitivity or exerting a compensatory restraint of feeding.

Objective The prevalence of antibodies in different organ-specific autoimmune diseases can vary depending on the racial group studied. Data on the prevalence of antibodies against steroidogenic enzymes in Addison's disease is available only for white Caucasians. We have evaluated the frequency of antibodies against adrenal cytoplasm, 21-hydroxylase, 17-alpha-hydroxylase and side-chain cleavage enzyme in a cohort of Indian patients with Addison's disease of idiopathic and granulomatous aetiology. Design Study of all patients with Addison's disease on whom serum samples were available (84% of total), presenting to the Endocrinology Department in a teaching hospital in India, between 1990 and 1999. Patients Thirty-eight patients with Addison's disease (19 idiopathic, 19 granulomatous). Methods A radiobinding assay using in vitro transcribed and translated recombinant human 35S-labelled 21-hydroxylase, 17-alpha-hydroxylase and side-chain cleavage enzymes was utilized to detect the respective antibodies. Adrenal cytoplasmic antibodies were measured by indirect immunofluorescence on cryostatic sections of human adrenal cortex. Results Of the 19 patients with idiopathic Addison's disease, adrenal cytoplasmic antibodies were present in five (26%) patients, while 21-hydroxylase antibodies were present in four (21%) subjects. The frequency of 21-hydroxylase antibodies was similar among patients with isolated idiopathic Addison's disease (3/13, 23%), and those associated with other organ-specific autoimmune diseases (1/6, 17%). 17-alpha-hydroxylase and side-chain cleavage antibodies were present in four (21%) and three (16%) patients, respectively. Overall, at least one of the three antibodies was present in eight (42%) subjects. All four female patients with premature ovarian failure had antibodies against 17-alpha-hydroxylase and/or side-chain cleavage enzyme. Two (11%) patients with granulomatous Addison's disease had adrenal antibodies. Of these, one patient with enlarged and calcified adrenal gland secondary to tuberculosis had a high titre of antibodies against all three steroidogenic enzymes. Conclusions Antibodies to 21-hydroxylase enzyme are less frequent in idiopathic Addison's disease in north Indians, when compared with other Caucasians. In contrast, the prevalence of 17-alpha-hydroxylase and side-chain cleavage enzyme antibodies is similar to those reported. High titre antibodies against steroidogenic enzymes may occasionally be present in patients with clinical evidence of tuberculous Addison's disease.

Inclusion body myopathy (IBM) is a myopathy causing asymmetric proximal and distal limb muscle involvement in patients over 50 years. Motor neuron disease (MND) is a neurodegenerative disorder involving upper and lower motor neuron in the spinal cord and brainstem, characterized by progressive muscle weakness resulting in paralysis. The pathogenesis of cell injury in both diseases is still unknown: several hypothesis have been proposed addressing viral, autoimmunity, genetic and oxidation stress factors. We report on 2 cases with clinical presentation of upper and/or lower motor neuron involvement and histopathological diagnosis of IBM. Case 1: a 68 years old man with an 18-month history of progressive weakness, spasticity, dysarthria, dysphagia. Neurological examination showed generalized muscle weakness, wasting of the finger flexors and quadriceps, fasciculations, deep tendon hyperreflexia. Electromyography (EMG) showed neurogenic signs and fasciculations at limbs and tongue muscles. Nerve conduction studies showed reduced cMAP amplitude at the legs, Motor Evoked Potential (MEP) revealed marked pyramidal tract involvement. Blood examination showed increased E.S.R. with normal level of serum creatinine kinase, copper, ceruloplasmin, and iron. Antiganglioside antibodies titer was normal and blood lactate analysis showed normal values during exercise. Cerebrospinal fluid (CSF) examination showed increased protein level. Brain magnetic resonance imaging disclosed of involvement of the cortico-spinal tract and deposits of paramagnetic material in the basal ganglia with normal dopaminergic receptorial SPECT binding. Muscle biopsy revealed a neurogenic myopathy with “rimmed vacuoles”. Case 2: a 64 years old woman with 20 month history of muscle weakness slowly progressing from upper to lower limbs. Neurological examination showed distal muscle weakness and wasting at the upper limbs, deep tendon hypo-areflexia. EMG showed neurogenic signs and fasciculations at four limbs. MEP and nerve conduction studies were normal but H reflex and F late responses were absent. E.S.R. was increased, while antiganglioside antibodies titer, thyroid hormones dosage and CSF examination were normal. Muscle biopsy revealed a neurogenic myopathy with rare “rimmed vacuoles”. These case reports, although not nosologically defined, confirm the clinical variability of the IBM and rise questions on the possible mechanisms of neuronal damage in motor neuron syndromes.

Summary objective The appearance of 21-hydroxylase autoantibodies (21OHAbs) identifies subjects with preclinical adrenal insufficiency. In 21OHAb-positive subjects, the adrenocortical function is best evaluated by peak cortisol (F) levels after the low-dose (1 µg) ACTH stimulation test (LDT). No information is currently available on the correlation between F and other adrenocortical hormone responses to the LDT in subjects with an ongoing autoimmune adrenal process. In this study, we tested the hypothesis that the dehydroepiandrosterone (DHEA), 17α-hydroxyprogesterone (17OHP) and aldosterone (A) responses to the LDT are consensual to that of F during the preclinical phase of autoimmune adrenal insufficiency. design and patients We studied 12 subjects positive for 21OHAb, in the absence of clinical signs of adrenal insufficiency. On the basis of peak F levels after the LDT, and according to the lower level of normal observed in 15 healthy volunteers (510·4 nmol/l), patients were subdivided into two groups: group A, n = 6 subjects with normal F response; and group B, n = 6 subjects with impaired F response. Results were expressed as absolute delta increase (Δ) between peak and basal levels. results ΔF was significantly higher in group A (314·5 ± 115·8 nmol/l) than in group B (151·7 ± 88·2 nmol/l) (P = 0·041). ΔDHEA and Δ17OHP were also significantly higher in group A (17·0 ± 13·5 nmol/l and 6·1 ± 4·4 nmol/l, respectively) than in group B (0·69 ± 2·25 nmol/l and 1·9 ± 1·7 nmol/l, respectively) (P = 0·002 and P = 0·041). The difference in ΔA between the two groups did not reach statistical significance (group A 321·8 ± 272·0 pmol/l vs. group B 157·0 ± 154·0 pmol/l). ΔDHEA, Δ17OHP and ΔA tended to correlate positively with ΔF (P = 0·039, P = 0·039 and P = 0·044, respectively), but the correlations did not reach significance after correction of the P-value. conclusions Our study demonstrates a high concordance between F and DHEA, 17OHP and A responses to the LDT in subjects with preclinical adrenal autoimmunity, thus strengthening the concept that the LDT is an accurate test to identify early adrenal dysfunction.

A general synthesis of a new class of optically active amino acids containing an oxazole moiety is described along with a strategy for their insertion into a peptidomimetic chain. A modified portion of endothelin-1 is prepared as a potential receptor antagonist. The procedure presented is based on readily available materials and can be performed in multigram quantities.

OBJECTIVE The presence of 21-hydroxylase autoantibodies (21OHAb) is a marker of adrenal autoimmunity and can be used to identify subjects with pre-clinical Addison's disease. The low-dose (1 μg) ACTH test (LDT) is more sensitive than the high-dose (250 μg) test (HDT) for the diagnosis of pituitary adrenal insufficiency, but no information is available on the use of a LDT in subjects with autoimmune adrenalitis and primary adrenal insufficiency. The aim of our study was to evaluate the clinical use of the LDT in the diagnosis of early adrenocortical dysfunction in patients with adrenal autoantibodies. DESIGN AND METHODS Firstly, we evaluated the cortisol responses to both a LDT and a HDT in a group of 12 healthy volunteers. We then performed a LDT in 11 subjects positive for 21OHAb, but without clinical signs of Addison's disease identified by screening 920 patients with one or more organ-specific autoimmune diseases. In all cases, the LDT was followed by a sequential HDT which was used as a control test of the sensitivity and specificity of the LDT. RESULTS In healthy subjects, the peak cortisol levels after the LDT were similar to those after the classical HDT. In 21OHAb-positive subjects, the LDT showed a pathological response in five out of 11 (45%) cases and the diagnostic concordance between the results of the LDT and those of the HDT was 100%. All the five cases with pathological LDT were also positive for adrenal cortex autoantibodies (ACA) and 4/5 had high levels of basal ACTH. One subject with pathological LDT developed clinical Addison's disease 4 months after the test had been performed. CONCLUSIONS Our study demonstrates that the low dose ACTH test has a high diagnostic sensitivity and specificity for primary adrenal insufficiency and suggests that it can accurately identify subjects with pre-clinical adrenal dysfunction.

OBJECTIVE Glutamic acid decarboxylase (GAD)65 autoantibodies (GAD65Ab) in type 2 diabetic subjects with secondary failure to sulphonylurea treatment identify the so-called latent autoimmune diabetes of the adult (LADA). The aim of our study was to estimate the risk for endocrine autoimmunity in type 2 diabetic subjects with GAD65Ab. DESIGN AND PATIENTS We analysed serum samples from 600 adult subjects with a clinical diagnosis of type 2 diabetes mellitus for the presence and levels of GAD65Ab and antibodies directed against the islet autoantigen IA-2/ICA512 (IA-2/ICA512Ab). All the patients had been treated initially with hypoglycaemic agents and/or diet for at least 1 year. GAD65Ab+ subjects were studied for the presence of thyroid peroxidase autoantibodies (TPOAb), 21 hydroxylase autoantibodies (21OHAb) and frequency of HLA class II haplotypes. RESULTS GAD65Ab were found in 67/600 (11%) and IA-2/ICA512Ab in 12/600 (2%) subjects (P

Most IDDM patients temporarily restore some of their beta-cell function following the initiation of insulin therapy. The aim of this study was to analyse the influence of age, gender, metabolic state at diagnosis and presence of autoantibodies (GAD65 antibodies and ICA) on the duration of the clinical partial remission. In total, 149 consecutively diagnosed IDDM children, 0-16 y old (70F, 79M, mean age 9.5 y) were studied. Partial remission was arbitrarily defined as the period when the insulin dose was below 0.5 U/BW 24 h-1 and HbA1c below 7.5%, and occurred in 119/149 patients with a duration between 1 and 38 months. Cox's regression analysis showed that the factors significantly associated with the duration of remission were age, gender, interaction between age and gender, ICA and a high initial HbA1c, whereas GAD65Ab had no influence. Young boys had the shortest remission period, while adolescent boys had the longest, as compared to young and adolescent girls. The ICA-negative patients (n = 42) had a longer remission period (median 9.7 months) than the ICA-positive children (n = 107; 5.0 months; p = 0.0001), regardless of GAD65Ab status. We speculate that the relative insulin resistance, which is more pronounced in pubertal girls than in boys, may be associated with a more rapid increase of exogenous insulin requirement. These findings are important when evaluating the effect of islet cell autoreactivity on the clinical course of IDDM in children.

General syntheses of 1-(2-pyridyl)alkylamines and N-methyl or N,N-dimethyl-1-(2-pyridyl)alkylamines from optically active α-amino acids are described. The presented procedures are based on catalyzed co-cyclotrimerization of the suitable nitriles with acetylene, which can be conducted without loss of optical purity

General and convenient syntheses of optically active 5-alkylpiperazine- 2-carboxylic acids are described. The methods are based on cyclization of L- or D-serine with α-amino acids and occur without loss of optical purity. The presented procedures are based on readily available starting materials and can be arranged for multigram quantities

A procedure for the preparation of optically active (2 R ,5 S )- and (2 S ,5 S )-2-Carboxy-1,4-diaza-[4.3.0]bicyclononane is described. The method is based on the reduction of diketopiperazines obtained from cyclization of Pro-L-Ser or Pro-D-Ser and occurs without loss of enantiomeric purity. The synthesis is based on readily available starting materials and can be easily arranged for multigram scale preparations.

The addition of γ-monosubstituted allylchromium(III) reagents to N-protected α-amino aldehydes proceeds in a stereoconvergent manner in contrast with the case of the unsubstituted reagents, where the stereoselectivity depends on the nature of the group bonded to the nitrogen. The chromium(III) reagent derived from 3-chloromethyl-2-trimethylsilyl-1-propene was used to prepare a C2 symmetric HIV-protease inhibitor.

The synthesis of a tetra-functionalized template based on a diketopiperazine skeleton is described together with some protocols for the synthesis of families of diversomers using a parallel synthesis approach.

Enantiospecific syntheses of optically active amino acids containing an oxazole moiety are described. Two different strategies for their insertion in a peptidomimetic chain are also discussed. The procedures presented are based on materials readily available in multigram quantities.

Several polyhydroxylated pyrrolidines with an aliphatic long chain on the ring nitrogen were prepared starting from d -mannitol. An amphiphilic bis-azasugar scaffold has been also prepared. These products behave as cationic surfactants and show a promising anti HIV-1 activity.

The synthesis of tri-functionalized orthogonally protected CRAB templates based on the triazine skeleton are described together with some protocols for the preparation of families of diversomers using a parallel synthesis approach.

A stereospecific syntheses of optically active pyrazoles and isoxazoles from L-proline is described. The procedure presented is based on readily available materials and can be used for preparing new conformationally restricted pyrazole-containing amino acids.

Methodology for preparing a series of novel α-amino-acids and their derivatives containing an isoxazole ring as a substituent is presented. The synthesis starts from a readily available l -serine derivative from which, depending on the synthetic strategy, it is possible to obtain isoxazol-3-yl or isoxazol-5-yl amino-acid precursors.