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Novel derivatives of poly(aspartic acid) conjugated with various amino acids and their amphiphilic copolymers were synthesized and characterized. Methyl esters of various amino acids (in their hydrochloride form) were synthesized from the reaction of amino acids with methanol in the presence of chlorotrimethylsilane (TMSCl). Aminolysis reaction onto polysuccinimide (PSI) using various amino acid methyl esters in the presence of catalyst and the followed hydrolysis provided the corresponding amino acid-conjugated poly(aspartic acid) derivatives in high reaction yield. Amino acid—conjugated amphiphilic analogs were also prepared by introducing hydrophobic alkylamine along with amino acid using a similar procedure. The chemical structures of copolymers were confirmed by FT-IR and 1H NMR spectroscopy. The physicochemical properties of amphiphilic copolymers were characterized using dynamic light scattering (DLS), fluorescence spectroscopy and field emission scanning electron microscopy (FE-SEM). In addition, the in vitro cell viability of the copolymers was examined. These polymers have potential applications in the pharmaceutical and cosmetic fields as delivery vehicles for bioactive molecules.

A direct solid-phase synthesis of a series of substituted benzimidazole-containing peptides is described. The method involves on-resin formation of new amino acids containing benzimidazole derivatives in the side chain. The heterocycle conjugates were obtained by reaction between aldehydes and peptides containing beta-(3,4-diaminophenyl)alanine residue, immobilized on a polymeric solid support.

We report on a simple synthetic route to a novel anthracene-based bis-armed amino acid derivative as a useful fluorescent probe. Various photophysical studies of this amino acid derivative are also described. Here, Suzuki-Miyaura cross-coupling reaction has been used as a key step for carbon-carbon bond formation.

Three kinds of poly amino acids, poly-γ-glutamic acid, poly(ɛ-L-lysine) and multi-L-arginyl-poly (L-aspartic acid) can be synthesized by enzymatic process independently from ribosomal protein biosynthesis pathways in microorganism. These biosynthesized polymers have attracted more and more attentions because of their unique properties and various applications. In this review, the current knowledge on the biosynthesis, biodegradations and applications of these three poly amino acids are summarized.

Entirely amino acid-based polymers were prepared by side-chain attachment to polysuccinimide derived from the thermal polycondensation of aspartic acid. Following deprotonation of various amino acid ester hydrochlorides by a secondary amine, the restored primary amino groups initiated the ring-opening of succinimide to form amide bonds. 1H and 13C NMR measurements revealed that the mole fraction of the introduced amino acid side chains could be controlled by the reaction time, while no hydrolysis of methyl ester groups was observed. The synthesized polymers contain exclusively amino acids, which makes them promising candidates as base materials of controlled drug delivery systems.

The proton coupled amino acid transporter PAT1 expressed in intestine, brain, and other organs accepts L- and D-proline, glycine, and L-alanine but also pharmaceutically active amino acid derivatives such as 3-amino-1-propanesulfonic acid, L-azetidine-2-carboxylic acid, and cis-4-hydroxy-D-proline as substrates. We systematically analyzed the structural requirements for PAT1 substrates by testing 87 amino acids, proline homologs, indoles, and derivatives. Affinity data and effects on membrane potential were determined using Caco-2 cells. For aliphatic amino acids, a blocked carboxyl group, the distance between amino and carboxyl group, and the position of the hydroxyl group are affinity limiting factors. Methylation of the amino group enhances substrate affinity. Hetero atoms in the proline template are well tolerated. Aromatic alpha-amino acids display low affinity. PAT1 interacts strongly with heterocyclic aromatic acids containing an indole scaffold. The structural requirements of PAT1 substrates elucidated in this study will be useful for the development of prodrugs.

We summarize here results of studies designed to elucidate basic mechanisms of reactive oxygen (ROS)-mediated oxidation of proteins and free amino acids. These studies have shown that oxidation of proteins can lead to hydroxylation of aromatic groups and aliphatic amino acid side chains, nitration of aromatic amino acid residues, nitrosylation of sulfhydryl groups, sulfoxidation of methionine residues, chlorination of aromatic groups and primary amino groups, and to conversion of some amino acid residues to carbonyl derivatives. Oxidation can lead also to cleavage of the polypeptide chain and to formation of cross-linked protein aggregates. Furthermore, functional groups of proteins can react with oxidation products of polyunsaturated fatty acids and with carbohydrate derivatives (glycation/glycoxidation) to produce inactive derivatives. Highly specific methods have been developed for the detection and assay of the various kinds of protein modifications. Because the generation of carbonyl derivatives occurs by many different mechanisms, the level of carbonyl groups in proteins is widely used as a marker of oxidative protein damage. The level of oxidized proteins increases with aging and in a number of age-related diseases. However, the accumulation of oxidized protein is a complex function of the rates of ROS formation, antioxidant levels, and the ability to proteolytically eliminate oxidized forms of proteins. Thus, the accumulation of oxidized proteins is also dependent upon genetic factors and individual life styles. It is noteworthy that surface-exposed methionine and cysteine residues of proteins are particularly sensitive to oxidation by almost all forms of ROS; however, unlike other kinds of oxidation the oxidation of these sulfur-containing amino acid residues is reversible. It is thus evident that the cyclic oxidation and reduction of the sulfur-containing amino acids may serve as an important antioxidant mechanism, and also that these reversible oxidations may provide an important mechanism for the regulation of some enzyme functions.

Peptide-chemistry methods have produced various amino-acid conjugates of 3-phenoxychromones in which 7-hydroxychromone is bound to the amino acid by the C- or N-terminus

We report the solid-phase synthesis and receptor-binding properties of eleven oxytocin analogs (Mpa-Xxx-Ile-Gln-Asn-Cys-Sar-Arg-Gly-NH2) containing non-coded amino acids in position 2: D-α- and L-α-(2-indanyl)glycine, R,S-6-methoxy-2-aminotetralin-2-carboxylic acid, D- and L-pentafluorophenylalanine, D,L-2,4-dimethylphenylalanine, D,L-2,4,6-trimethylphenylalanine, R,R- and S,S-1,2,3,4-tetrahydro-1-methyl-β-carboline-3-carboxylic acid and R- and S-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid. Some of these amino acid analogs (2-indanylglycine and D-pentafluorophenylalanine) were earlier successfully applied for the synthesis of potent bradykinin antagonists [1,2]. Their receptor bindings were tested on isolated guinea-pig uterus, rat liver and rat kidney inner medulla plasma membranes. The extent of binding of the peptides to the oxytocin receptor was in several cases was even higher than that of the parent hormone (oxytocin). However, the real pharmacological value of these analogs can be evaluated only after in vivo measurements of their inhibition of uterine motor activity.

In vitroevolution is used to study protein sequences, structures, and interactions and to obtain proteins with new properties. To analyze the specific features of this process in phage display experiments, we studied the amino acid composition of selected sequences, constructed a matrix of amino acid substitutions, and identified pairs of coadaptive substitutions. The amino acid frequency proved to be tightly associated with the number of corresponding codons; numerous correlated substitutions were found.

Novel endomorphin-2 analogs containing the unusual amphiphilic amino acid (R)- and (S)-α-hydroxymethyltyrosine in position 1 and (R)- and (S)-α-hydroxymethylphenylalanine in the positions 3 and 4 were synthesized via the solid-phase method. The binding characteristics of the synthetic analogs may suggest that α-hydroxymethyl substitution of amino acid residues influences the conformation of a peptide much more than simply increasing the local amphiphilic character of the peptide.

A number of 7-O-aminoacyl derivatives of isoflavones have been obtained by the interaction of 2-R-7-hydroxy-3′,4′-ethylenedioxyisoflavones with the symmetrical anhydrides of N-protected amino acids.

The proteins synthesized in vitro by the nuclei of animal and plant cells differ in their amino acid compositions. The differences found show the species specificity of the products.

Background Despite the importance of β-strands as main building blocks in proteins, the propensity of amino acid in β-strands is not well-understood as it has been more difficult to determine experimentally compared to α-helices. Recent studies have shown that most of the amino acids have significantly high or low propensity towards both ends of β-strands. However, a comprehensive analysis of the sequence dependent amino acid propensities at positions between the ends of the β-strand has not been investigated. Results The propensities of the amino acids calculated from a large non-redundant database of proteins are found to be highly position-specific and vary continuously throughout the length of the β-strand. They follow an unexpected characteristic periodic pattern in inner positions with respect to the cap residues in both termini of β-strands; this periodic nature is markedly different from that of the α-helices with respect to the strength and pattern in periodicity. This periodicity is not only different for different amino acids but it also varies considerably for the amino acids belonging to the same physico-chemical group. Average hydrophobicity is also found to be periodic with respect to the positions from both termini of β-strands. Conclusions The results contradict the earlier perception of isotropic nature of amino acid propensities in the middle region of β-strands. These position-specific propensities should be of immense help in understanding the factors responsible for β-strand design and efficient prediction of β-strand structure in unknown proteins.

In this work we described the synthesis of the 8-dimethylaminoethyl ester of N-benzy!oxycarbonylglycine (I) by an imidazole method, by the method of mixed anhydrides, and by the method of activated esters. At the same time we investigated the possibility of using the l-methyl-2-ethoxycarbonylvinyl (MEV) N-protective group for the synthesis of 8-dimethylaminoethyl and choline esters of amino acids.

Enzymatic Cleavage of Amino Terminal Methionine from Recombinant Human Interleukin 2 and Growth Hormone by Aminopeptidase M

The basic fraction of the acid-labile amino acid precursors found in hot water extracts of the Murchison meteorite was treated with ninhydrin under conditions that give destruction of free amino acids but allow nearly complete recovery to peptides and amino acylamides. After this treatment and a subsequent acid hydrolysis, the amount of amino acids found corresponded to less than 30 per cent of the precursor content of the basic fraction. Since only 30 percent of the total extract precursors are found in the basic fraction, these results indicate that such compounds, if present, account for no more than 9 mole per cent of the total acid-labile amino acid precursors of the meteorite hot water extract.

Interaction based on possible chemical affinity of an amino acid for tRNA was examined as a model for the aminoacylation of primitive tRNA without aid of an enzyme system. Two types of reaction were carried out and compared. One was the acyl linkage of amino acid to the 5'-terminal phosphate of a tRNA activated as an imidazolide. The other was the incorporation of an amino acid activated as an imidazolide into 2'(3')-hydroxyl groups of intact tRNA. Both types of reaction indicated that none of the amino acids tested had any selectivity for the tRNAs examined. However, the rates of reaction with a given tRNA were different among amino acids. In the second type of reaction, amino acids were found mainly at loop-out regions of tRNA, but not at either its 5'- or 3'-terminal sites.

A number of melatonin analogs, containing dichloroacetic acid and various amino acid residues instead of an acetic acid residue, were synthesized.

1. A method for obtaining amino acid and peptide derivatives of α-methyltryptamine have been described.

THE Streptomyces antibiotic A23187, a divalent cation ionophore1, has been used as a tool in studies of the role of calcium in several cellular phenomena2–5. A23187 has a much higher affinity for divalent than monovalent cations, and the increased permeability induced by this ionophore in cellular membranes favours calcium and magnesium. X537A, another divalent cation ionophore6, also enhances fluxes of monovalent cations7 and forms lipid-soluble complexes with noradrenaline and some other organic compounds8. A23187 has often been referred to as a specific divalent cation ionophore although, to our knowledge, the evidence for the specificity is restricted to the lack of interaction with common monovalent cations like sodium and potassium1,2. In this paper we report experiments which show that A23187 is able to form lipid-soluble complexes with leucine and other amino acids at concentrations as low as or lower than those needed to form similar complexes with calcium.

Synthetic routes to and the properties of N-(2-chloro-5-fluoro-4-pyrimidyl)- and N-(2-ethylthio-5-fluoro-4-pyrimidyl)-substituted amino acids are shown.

2H-TaS2 can be intercalated by organic amines and empirical rules have been formulated1–3 governing the properties that chemical species must possess in order to intercalate. One of these rules is that molecules in which the nitrogen is basic (pKa>4) usually form stable compounds provided the amine does not have bulky substituents. For certain amino acids, the values of pKa are significantly larger than this critical value (for example, glycine pK2=9.78)5 so that if the zwitterion is in a state where it can function as a base, it might be expected that the amino acid would intercalate 2H-TaS2. This prediction has been verified for a number of amino acids. The discovery of these intercalation reactions provides a new range of intercalated compounds for study and also opens up the possibility of in situ polymerisation.

THE main problem in working out the structure of peptides is to establish their amino-acid sequence. An essential part of this task consists in determining the amino-terminal and carboxyl-terminal amino-acid residues of the peptide chain (the amino-acid and the amino-acid)1. Many methods are dealing with this problem2.

A NEW amino-acid, N e-(2-amino-2-carboxyethyl)-lysine, in acid hydrolysates of alkali-treated proteins has been reported1,2. The trivial name lysinoalanine was chosen for this compound, which is probably formed by the addition of an amino group of a lysyl residue at the double bond of a dehydroalanyl residue formed after alkaline decomposition of disulphide bonds. Lysinoalanine has been synthesized by two different methods1,3 in order to confirm its chemical structure.