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Nessa pesquisa, foram avaliadas diferentes concentrações do pó do resíduo sólido da hidrodestilação da folha de pimenta rosa (PRHPPL), gerado na produção de seu óleo essencial, como inibidor para aço carbono em HCl 0,5 mol L-1. Esta avaliação foi realizada por meio de espectroscopia de impedância eletroquímica (EIS), polarização potenciodinâmica, técnica de varredura de eletrodo vibratório (SVET) e testes de perda de massa. Todos os testes mostraram que a maior concentração do inibidor (1,77 g L-1) apresentou melhor eficiência; do icorr, essa eficiência foi de 98%, do modelo de circuito equivalente Rct valor foi de 98% e pelo teste gravimétrico foi de 86%. Diferentes isotermas foram testadas a fim de entender melhor o processo de adsorção das moléculas inibidoras na superfície do metal e o melhor ajuste foi encontrado para a isoterma de Langmuir. A morfologia da superfície do aço também foi analisada por microscopia eletrônica de varredura (MEV). Este estudo revela que este resíduo obtido da produção de óleos essenciais pode ser utilizado como inibidor de corrosão em substituição aos inibidores sintéticos. En esta investigación, se evaluaron diferentes concentraciones del polvo del residuo sólido de la hidrodestilación de la hoja de ají rosa (PRHPPL), generado en la producción de su aceite esencial, como inhibidor del acero al carbono en HCl 0.5 mol L-1. Esta evaluación se realizó mediante espectroscopia de impedancia electroquímica (EIS), polarización potenciodinámica, técnica de exploración de electrodos vibratorios (SVET) y pruebas de pérdida de masa. Todas las pruebas mostraron que la mayor concentración del inhibidor (1.77 g L-1) presentó mejor eficiencia; de icorr, esta eficiencia fue del 98 %, del modelo de circuito equivalente valor Rct fue del 98 % y por la prueba gravimétrica fue del 86 %. Se probaron diferentes isotermas para comprender mejor el proceso de adsorción de las moléculas inhibidoras en la superficie del metal y se encontró el mejor ajuste para la isoterma de Langmuir. La morfología de la superficie del acero también se analizó mediante microscopía electrónica de barrido (SEM). Este estudio revela que este residuo obtenido de la producción de aceites esenciales puede ser utilizado como inhibidor de corrosión en reemplazo de inhibidores sintéticos. In this research, different concentrations of the powder of the solid residue from the hydrodistillation of the pink pepper leaf (PRHPPL), generated in the production of its essential oil, were evaluated as an inhibitor for carbon steel in HCl 0.5 mol L-1. This evaluation was performed using electrochemical impedance spectroscopy (EIS), potentiodynamic polarization, scanning vibrating electrode technique (SVET), and mass loss tests. All tests showed that the highest concentration of the inhibitor (1.77 g L-1) presented better efficiency; from icorr, this efficiency was 98 %, from the equivalent circuit model Rct value it was 98 % and by the gravimetric test it was 86 %. Different isotherms were tested in order to better understand the adsorption process of the inhibitor molecules on the metal surface and the best fit was found for the Langmuir isotherm. The morphology of the steel surface was also analyzed by scanning electron microscopy (SEM). This study reveals that this residue obtained from the production of essential oils can be used as corrosion inhibitor in the replacement to synthetic inhibitors.

Osteosarcoma is one of the most common types of bone cancers among paediatric patients. Despite the advances made in surgery, chemo-, and radiotherapy, the mortality rate of metastatic osteosarcoma remains unchangeably high. The standard drug combination used to treat this bone cancer has remained the same for the last 20 years, and it produces many dangerous side effects. Through history, from ancient to modern times, nature has been a remarkable source of chemical diversity, used to alleviate human disease. The application of modern scientific technology to the study of natural products has identified many specific molecules with anti-cancer properties. This review describes the latest discovered anti-cancer compounds extracted from traditional medicinal plants, with a focus on osteosarcoma research, and on their cellular and molecular mechanisms of action. The presented compounds have proven to kill osteosarcoma cells by interfering with different pathways: apoptosis induction, stimulation of autophagy, generation of reactive oxygen species, etc. This wide variety of cellular targets confer natural products the potential to be used as chemotherapeutic drugs, and also the ability to act as sensitizers in drug combination treatments. The major hindrance for these molecules is low bioavailability. A problem that may be solved by chemical modification or nano-encapsulation.

The malt bagasse is a solid residue, highly produced in the brewing industry. The presence of high levels of antioxidants in its composition makes this residue an attractive possibility as a corrosion inhibitor, besides being a sustainable and low cost alternative to the inorganic procedures currently used to prevent corrosion. In this sense, this work evaluated the efficiency of the malt bagasse powder as a corrosion inhibitor on the surface of AISI 1020 carbon steel, in different concentrations, in acidic medium 0.5 mol.L-1 HCl. The resistance to corrosion was tested by electrochemical techniques, such as electrochemical impedance spectroscopy (EIS) and anodic and cathodic polarization curves. The efficiency of the corrosion inhibitor was evaluated by weight loss tests. Fourier transform infrared spectroscopy (FTIR) and optical microscope surface image analysis were respectively used as chemical and morphological characterization techniques, respectively. From the EIS results, it can be said that the powder has its efficiency increased once the concentration is higher. On the other hand, the polarization curves shows the malt bagasse powder as an inhibitor presents both anodic and cathodic behavior. The weight loss results confirmed the electrochemical results, showing 92.5% efficiency for the 1.77 g.L-1 concentration. The adsorption isotherm on the steel surface follows Languimir’s Isotherm. The FTIR analysis indicates the presence of heteroatoms such as C, N, O, incorporated in functional groups that could be responsible for the inhibitory properties found in the powder. The images obtained from the optical microscope, showed that the corrosion process, in the presence of the inhibitor in the electrolyte, is retarded. Therefore, the results indicate that the malt bagasse powder has the potential to be a corrosion inhibitor for steel in acidic medium, adding value in the beer production chain.

Thrombin is the key enzyme of the entire hemostatic process since it is able to exert both procoagulant and anticoagulant functions; therefore, it represents an attractive target for the developments of biomolecules with therapeutic potential. Thrombin can perform its many functional activities because of its ability to recognize a wide variety of substrates, inhibitors, and cofactors. These molecules frequently are bound to positively charged regions on the surface of protein called exosites. In this review, we carried out extensive analyses of the structural determinants of thrombin partnerships by surveying literature data as well as the structural content of the Protein Data Bank (PDB). In particular, we used the information collected on functional, natural, and synthetic molecular ligands to define the anatomy of the exosites and to quantify the interface area between thrombin and exosite ligands. In this framework, we reviewed in detail the specificity of thrombin binding to aptamers, a class of compounds with intriguing pharmaceutical properties. Although these compounds anchor to protein using conservative patterns on its surface, the present analysis highlights some interesting peculiarities. Moreover, the impact of thrombin binding aptamers in the elucidation of the cross-talk between the two distant exosites is illustrated. Collectively, the data and the work here reviewed may provide insights into the design of novel thrombin inhibitors.

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) - coronavirus disease 2019 (COVID-19) has raised a severe global public health issue and creates a pandemic situation. The present work aims to study the molecular -docking and dynamic of three pertinent medicinal plants i.e. Eurycoma harmandiana, Sophora flavescens and Andrographis paniculata phyto-compounds against SARS-COV-2 papain-like protease (PLpro) and main protease (Mpro)/3-chymotrypsin-like protease (3CLpro). The interaction of protein targets and ligands was performed through AutoDock-Vina visualized using PyMOL and BIOVIA-Discovery Studio 2020. Molecular docking with canthin-6-one 9-O-beta-glucopyranoside showed highest binding affinity and less binding energy with both PLpro and Mpro/3CLpro proteases and was subjected to molecular dynamic (MD) simulations for a period of 100ns. Stability of the protein-ligand complexes was evaluated by different analyses. The binding free energy calculated using MM-PBSA and the results showed that the molecule must have stable interactions with the protein binding site. ADMET analysis of the compounds suggested that it is having drug-like properties like high gastrointestinal (GI) absorption, no blood-brain barrier permeability and high lipophilicity. The outcome revealed that canthin-6-one 9-O-beta-glucopyranoside can be used as a potential natural drug against COVID-19 protease., Graphical abstract Image 1

To improve the processing quality of potatoes, phosphate buffer extract (PBE), 50% ethanol (E50), and aqueous extract (AE) of tartary buckwheat seedlings were evaluated for their ability to inhibit the enzymatic browning of potatoes. The results suggest that all extracts of tartary buckwheat seedlings exert significant inhibitory effects on the polyphenol oxidase (PPO) activity in potatoes. The relative concentrations required for a 50% reduction in the PPO activity (IC50) were 0.21, 0.28 and 0.41 mg mL−1, for PBE, E50 and AE, respectively. The strongest inhibitory activity was observed for PBE, followed by E50 and AE. Four flavone compounds in the PBE of tartary buckwheat seedlings (i.e., rutin, kaempferol-3-O-rutinoside, quercetin, and kaempferol) were identified by high-performance liquid chromatography. These compounds were subsequently evaluated for their roles in the inhibition of PPO from potatoes using a model system. The results indicated that rutin exhibited the highest inhibition rate on the PPO of potato. A synergistic inhibitory effect was observed by mixing rutin, kaempferol-3-O-rutinoside, quercetin, and proteins. The inhibitory patterns of rutin, kaempferol-3-O-rutinoside, and quercetin on the enzyme were noncompetitive and reversible, with inhibitory constants of 0.12, 0.31, and 0.40 mg mL−1, respectively. Flavonoids from tartary buckwheat seedlings may exhibit a common mechanism with phenolic compounds, involving the blockage of the reaction of oxygen with PPO leading to the inhibition of the enzymes involved in browning. Based on these results, extracts of tartary buckwheat seedlings can be used as potent natural inhibitors.

The corrosion inhibition of mild steel by aqueous extract of cumaru (Dipteryx odorata) seeds and its high molecular weight fraction (HMWF) was investigated in 1 mol L-1 HCl solution. The study was carried out through gravimetric essays, open circuit potential measurements, anodic and cathodic polarization curves and electrochemical impedance analyses, as well as morphological analysis of the mild steel by scanning electron microscopy. Gravimetric tests showed that the inhibition efficiency (IE) increased with immersion time and inhibitor concentration, reaching 98% of IE using 100 mg L-1 of the HMWF, after 6 h immersion time. The activation energy (Ea) increased with the addition of both inhibitors which characterizes a physical adsorption of the constituents of the aqueous extract of cumaru on the metal surface. Polarization curves indicated that both aqueous cumaru seeds extract and its HMWF act as mixed-type inhibitor. Impedance results showed a decrease in double layer capacitance (Cdl) and an increase in charge transfer resistance (Rct) evidencing a typically screening effect. The adsorption of molecules present in the aqueous extract of cumaru followed the Langmuir isotherm. The aqueous cumaru seeds extract was characterized by Fourier transform infrared spectroscopy (FTIR), 1H, 13C and 2D nuclear magnetic resonance (NMR).

Mushrooms are attractive resources for novel enzymes and bioactive compounds. Nevertheless, mushrooms spontaneously form brown pigments during food processing as well as extraction procedures for functional compounds. In this study, the dark browning pigment in the extract derived from the edible mushroom Hericium erinaceus was determined to be caused by the oxidation of endogenous polyphenol compounds by the polyphenol oxidase (PPO) enzyme family. These oxidized pigment compounds were measured quantitatively using a fluorospectrophotometer and, through chelation deactivation and heat inactivation, were confirmed to be enzymatic browning products of reactions by a metalloprotein tyrosinase in the PPO family. Furthermore, a transcript analysis of the identified putative PPO-coding genes in the different growth phases showed that tyrosinase and laccase isoenzymes were highly expressed in the mushroom fruiting body, and these could be potential PPOs involved in the enzymatic browning reaction. A metabolite profiling analysis of two different growth phases also revealed a number of potential enzymatic browning substances that were grouped into amino acids and their derivatives, phenolic compounds, and purine and pyrimidine nucleobases. In addition, these analyses also demonstrated that the mushroom contained a relatively high amount of natural antioxidant compounds that can effectively decrease the browning reaction via PPO-inhibitory mechanisms that inhibit tyrosinase and scavenge free radicals in the fruiting body. Altogether, these results contribute to an understanding of the metabolites and PPO enzymes responsible for the enzymatic browning reaction of H. erinaceus.

Mushrooms are attractive resources for novel enzymes and bioactive compounds. Nevertheless, mushrooms spontaneously form brown pigments during food processing as well as extraction procedures for functional compounds. In this study, the dark browning pigment in the extract derived from the edible mushroom Hericium erinaceus was determined to be caused by the oxidation of endogenous polyphenol compounds by the polyphenol oxidase (PPO) enzyme family. These oxidized pigment compounds were measured quantitatively using a fluorospectrophotometer and, through chelation deactivation and heat inactivation, were confirmed to be enzymatic browning products of reactions by a metalloprotein tyrosinase in the PPO family. Furthermore, a transcript analysis of the identified putative PPO-coding genes in the different growth phases showed that tyrosinase and laccase isoenzymes were highly expressed in the mushroom fruiting body, and these could be potential PPOs involved in the enzymatic browning reaction. A metabolite profiling analysis of two different growth phases also revealed a number of potential enzymatic browning substances that were grouped into amino acids and their derivatives, phenolic compounds, and purine and pyrimidine nucleobases. In addition, these analyses also demonstrated that the mushroom contained a relatively high amount of natural antioxidant compounds that can effectively decrease the browning reaction via PPO-inhibitory mechanisms that inhibit tyrosinase and scavenge free radicals in the fruiting body. Altogether, these results contribute to an understanding of the metabolites and PPO enzymes responsible for the enzymatic browning reaction of H. erinaceus.

The use of corrosion inhibitors is one of the most common methods to combat acid corrosion. The current studies aim to apply natural products as corrosion inhibitors, once the most used compounds are mostly toxic to the environment and to humans. The present paper purposes the application of an aqueous extract of agro-industrial waste (AEAW) to inhibit the corrosion of stainless steel AISI 304 in sulfuric acid. Gravimetric and electrochemical experiments were performed. The gravimetric experiments revealed that the extract acts as an inhibitor for stainless steel, showing inhibitory efficiency up to 81.6%. The electrochemical tests show that the AEAW makes the steel surface more noble. The extract acts by adsorption in the metallic surface, following a Temkin isotherm. The results indicate that the AEAW is a promising substitute of conventional organic compounds as a corrosion inhibitor to AISI 304 stainless steel in sulfuric acid.

Cast iron has stood for centuries of invention. It is a very versatile and durable material. Coating systems are a low-maintenance protection method. The purpose of this research is to increase the Paraloid coating&rsquo, s resistance when applied to iron in high humidity atmospheres, with the addition of caffeine (1,3,7-dimethylxanthine) and nicotine (S)-3-(1-methylpyrrolidin-2-yl) pyridine as corrosion inhibitors, the resistance of protection versus exposure time will be evaluated by using electrochemical noise. A statistical analysis of the electrochemical noise signals was carried out. Recurrence plots were used as a powerful tool in the analysis to complement the data obtained and they predicted the evaluation of coatings behaviors performance versus time. The outcomes show that the addition of inhibitors increases and improves the performance as a temporary protection of Paraloid and that protection in high relative humidity was improved. Recurrence plots and parameter quantification show the variances in the surface corrosion dynamics.

RESUMO Os inibidores naturais são obtidos a partir de extratos de plantas ou de material biodegradável e acarretam a redução da intensidade de dissolução dos metais, diminuindo a sua taxa de corrosão. Pesquisas realizadas nos últimos anos relatam que muitos vegetais apresentam, em sua constituição, compostos com ação antioxidante, principalmente polifenóis. Nesse trabalho, será apresentado o histórico do desenvolvimento de inibidores naturais a partir de extratos de frutas para aplicação em meios neutros e ácidos realizado no Laboratório de Corrosão da COPPE, Labcorr/COPPE/UFRJ. Os extratos analisados foram casca de laranja, casca de manga, casca de maracujá, casca de caju, semente de mamão e bagaço de uva. Os extratos foram obtidos por três metodologias diferentes de extração: extração por infusão, extração por gradiente de polaridade e extração hidroalcoólica. As eficiências de inibição dos extratos testados foram obtidas através de ensaios de perda de massa. O meio neutro estudado simula a composição da água dos sistemas de resfriamento industrial com elevado ciclo de concentração, com 1050 ppm de cloreto, 450 ppm de íon cálcio e 160 ppm de íon bicarbonato e com pH 7,5. Os extratos tiveram um bom desempenho nos dois meios estudados. O extrato concentrado de bagaço de uva teve a melhor eficiência de inibição nos ensaios de perda de massa em 72 horas de imersão no meio neutro, cujo valor foi 74%. A eficiência dos inibidores estudados foi mais significativa em meio de ácido clorídrico 1 mol·L-1, com eficiências superiores a 93% em 24 horas de imersão. ABSTRACT The corrosion inhibitors are obtained from natural plant extracts or biodegradable material, and cause a reduction in the intensity of dissolution of metals by lowering their corrosion. Research conducted in recent years report that many plants have, in their constitution, compounds with antioxidant activity, mainly polyphenols. This paper will present the history of the development of natural inhibitors from fruit extracts for application in neutral and acid media carried out in Labcorr / COPPE / UFRJ. The orange peel, mango peel, passion fruit peel, cashew peel, papaya seed and grape pomace extracts were analyzed. The extracts were obtained by three different extraction methodologies: infusion extraction, polarity gradient extraction and hydroalcohol extraction. The inhibition efficiencies of the extracts tested were obtained by weight- loss tests. The neutral medium studied simulates the composition of water of industrial cooling systems with high concentration cycle, with 1050 ppm of chloride, 450 ppm of calcium and 160 ppm of bicarbonate and pH 7.5. The performance of extracts was good in both media studied. The concentrated grape pomace extracts had the best inhibition efficiency in the weight-loss tests with a period of 72 hours of immersion in neutral medium, whose value was of 74%. The efficiency of these inhibitors was more significant in 1 mol·L-1 hydrochloric acid media, with efficiencies above 93% in a period of 24 hours of immersion.

Guar gum (GG) was investigated as a possible eco-friendly corrosion inhibitor for pure aluminium in a 1-M HCl solution at different temperatures and immersion times using gravimetric and electrochemical techniques. The results showed that GG was a good corrosion inhibitor for pure aluminium in the studied environment. The inhibition efficiency of GG increased with increasing inhibitor concentration and immersion time but decreased with increasing temperature. Polarisation measurements revealed that GG was a mixed type inhibitor with a higher influence on the cathodic reaction. The adsorption behaviour of the investigated inhibitor was found to obey the Temkin adsorption isotherm and the calculated values of the standard free adsorption energy indicate mixed-type adsorption, with the physical adsorption being more dominant. The associated activation energy (Ea) and the heat of adsorption (Qa) supported the physical adsorption nature of the inhibitor. Fourier-transform infrared spectroscopy (FTIR) and Raman/SERS were used to explain the adsorption interaction between the inhibitor with the surface of the metal. The results suggested that most inhibition action of GG is due to its adsorption of the metal surface via H-bond formation.

Background Interaction of the small peptide hormone glucagon with glucagon receptor (GCGR) stimulates the release of glucose from the hepatic cells during fasting; hence GCGR performs a significant function in glucose homeostasis. Inhibiting the interaction between glucagon and its receptor has been reported to control hepatic glucose overproduction and thus GCGR has evolved as an attractive therapeutic target for the treatment of type II diabetes mellitus. Results In the present study, a large library of natural compounds was screened against 7 transmembrane domain of GCGR to identify novel therapeutic molecules that can inhibit the binding of glucagon with GCGR. Molecular dynamics simulations were performed to study the dynamic behaviour of the docked complexes and the molecular interactions between the screened compounds and the ligand binding residues of GCGR were analysed in detail. The top scoring compounds were also compared with already documented GCGR inhibitors- MK-0893 and LY2409021 for their binding affinity and other ADME properties. Finally, we have reported two natural drug like compounds PIB and CAA which showed good binding affinity for GCGR and are potent inhibitor of its functional activity. Conclusion This study contributes evidence for application of these compounds as prospective small ligand molecules against type II diabetes. Novel natural drug like inhibitors against the 7 transmembrane domain of GCGR have been identified which showed high binding affinity and potent inhibition of GCGR

Aminopeptidase N (APN)/CD13 (EC 3.4.11.2) is a transmembrane protease present in a wide variety of human tissues and cell types (endothelial, epithelial, fibroblast, leukocyte). APN/CD13 expression is dysregulated in inflammatory diseases and in cancers (solid and hematologic tumors). APN/CD13 serves as a receptor for coronaviruses. Natural and synthetic inhibitors of APN activity have been characterized. These inhibitors have revealed that APN is able to modulate bioactive peptide responses (pain management, vasopressin release) and to influence immune functions and major biological events (cell proliferation, secretion, invasion, angiogenesis). Therefore, inhibition of APN/CD13 may lead to the development of anti‐cancer and anti‐inflammatory drugs. This review provides an update on the biological and pharmacological profiles of known natural and synthetic APN inhibitors. Current status on their potential use as therapeutic agents is discussed with regard to toxicity and specificity. © 2005 Wiley Periodicals, Inc. Med Res Rev

The main objective of this work is to study the behavior of copper corrosion in nitric acid medium (2 M) for the evaluation and comparison of the corrosive power of the essential oil of Thymus Satureoides. To do this, we used weight loss and polarization techniques. The results show that the recovery rate of copper corrosion decreases in the presence of the essential oil tested. In a second step, we performed tests on the major component of the oil and the results obtained showed that the activity of the essential oil of thyme is clearly not related to it’s major constituent. On the other hand, it is clear from this study that the inhibition efficiency increases with the concentration of inhibitors to reach 89.04% at 1200 ppm for the essential oil of thyme and 69.72% at 1600 ppm for borneol. The adsorption isotherm and the activation energy were also determined.

The structure of F 1 -ATPase from Saccharomyces cerevisiae inhibited by the yeast IF 1 has been determined at 2.5 Å resolution. The inhibitory region of IF 1 from residues 1 to 36 is entrapped between the C-terminal domains of the α DP - and β DP -subunits in one of the three catalytic interfaces of the enzyme. Although the structure of the inhibited complex is similar to that of the bovine-inhibited complex, there are significant differences between the structures of the inhibitors and their detailed interactions with F 1 -ATPase. However, the most significant difference is in the nucleotide occupancy of the catalytic β E -subunits. The nucleotide binding site in β E -subunit in the yeast complex contains an ADP molecule without an accompanying magnesium ion, whereas it is unoccupied in the bovine complex. Thus, the structure provides further evidence of sequential product release, with the phosphate and the magnesium ion released before the ADP molecule.

In this study we examined surface expression of CD26 and the corresponding enzyme activity of dipeptidyl peptidase IV (DPPIV) on the cells of immature murine T-cell line, R1.1. The data obtained have shown that R1.1 cells express high density of surface CD26 as compared to normal thymus cells. This was associated with strong enzyme activity, which, based on substrates and inhibitor specificity, corresponded to DPPIV. The DPPIV enzyme activity of R1.1 cells was 10 times stronger than that found on normal murine thymus cells (V(max) = 39 micromol/min/10(6) cells, vs 3.7 micromol/min/10(6) cells, respectively). Upon activation with anti-CD3, up-regulation of both membrane CD26, as well as of DPPIV enzyme activity on R1.1 cells were observed. The finding of strong DPPIV on R1.1 cells makes them suitable model for testing putative substrates/inhibitors of the enzyme in its natural microenvironment. Since in addition to strong DPPIV, R1.1 cells also express kappa opioid receptors (KOR) [European Journal of Pharmacology 227 (1992) 257], we tested the effect of dynorphin-A(1-17), an endogenous opioid peptide with KOR selectivity, on DPPIV of R1.1 cells. Dynorphin-A(1-17) down-regulated DPPIV in a dose-dependent manner, with the potency similar to that of substance P, a known natural DPPIV substrate [Journal of Pharmacology and Experimental Therapeutics 260 (1992) 1257]. DPPIV down-regulation was resistant to bestatin and thiorphan, the inhibitors of two cell surface peptidases (APN and NEP, respectively) with potential of dynorphin-A(1-17) degradation, suggesting that the mechanism underlying the observed effect does not involve degradative products of dynorphin-A(1-17). DPPIV down-regulation was also resistent to KOR antagonist, NBI, suggesting that the mechanism underlying the observed phenomenon involves neither cointernalization of KOR and DPPIV. Collectively, cells of immature T cell line, R1.1 exert strong DPPIV enzyme activity, which could be down-regulated in the presence of dynorphin-A(1-17) by mechanism that presumably includes non-substrate inhibition. By down-regulating DPPIV, dynorphin-A(1-17) may indirectly affect activity and/or specificity of natural substrates of DPPIV, such as substance P, RANTES, and endomorphins.