Abstract
A number of monocyclic SFTI-1 analogues modified in the conserved inhibitor P1 position by Pro, its L-hydroxyproline (Hyp) derivative as well as mimetics with different ring size were synthesized by the solid-phase method. Replacement of Ser6 by Pro, Hyp, and a four-member ring, L-azetidine-2-carboxylic acid (Aze), retained trypsin or chymotrypsin inhibitory activity. The determined association equilibrium constants of these analogues with a cognate enzyme were about two orders of magnitude lower than those obtained for ones with conserved Ser6. In all analogues, with the exception of one, [Phe5,Aze6]SFTI-1, the P1-P1 reactive site remained intact. The results provide first evidence that the conserved Ser in the P1 position of Bowman-Birk inhibitors can be successfully replaced by an amino acid with a secondary amine group.
Keywords: Peptides, proteinase inhibitors, SFTI-1, mimetics of Pro, BB, BBI, Fmoc, DCM, DMF/NMP, NPGB, MALDI MS, BAPNA, HPLC, Proteolytic susceptibilityPeptides, proteinase inhibitors, SFTI-1, mimetics of Pro, BB, BBI, Fmoc, DCM, DMF/NMP, NPGB, MALDI MS, BAPNA, HPLC, Proteolytic susceptibility
Protein & Peptide Letters
Title: Introduction of Pro and Its Analogues in the Conserved P1 Position of Trypsin Inhibitor SFTI-1 Retains Its Inhibitory Activity
Volume: 18 Issue: 11
Author(s): Anna Legowska, Dawid Debowski, Rafal Lukajtis, Emilia Sztabkowska, Aneta Mizeria, Krzysztof Brzozowski, Magdalena Wysocka, Adam Lesner and Krzysztof Rolka
Affiliation:
Keywords: Peptides, proteinase inhibitors, SFTI-1, mimetics of Pro, BB, BBI, Fmoc, DCM, DMF/NMP, NPGB, MALDI MS, BAPNA, HPLC, Proteolytic susceptibilityPeptides, proteinase inhibitors, SFTI-1, mimetics of Pro, BB, BBI, Fmoc, DCM, DMF/NMP, NPGB, MALDI MS, BAPNA, HPLC, Proteolytic susceptibility
Abstract: A number of monocyclic SFTI-1 analogues modified in the conserved inhibitor P1 position by Pro, its L-hydroxyproline (Hyp) derivative as well as mimetics with different ring size were synthesized by the solid-phase method. Replacement of Ser6 by Pro, Hyp, and a four-member ring, L-azetidine-2-carboxylic acid (Aze), retained trypsin or chymotrypsin inhibitory activity. The determined association equilibrium constants of these analogues with a cognate enzyme were about two orders of magnitude lower than those obtained for ones with conserved Ser6. In all analogues, with the exception of one, [Phe5,Aze6]SFTI-1, the P1-P1 reactive site remained intact. The results provide first evidence that the conserved Ser in the P1 position of Bowman-Birk inhibitors can be successfully replaced by an amino acid with a secondary amine group.
Export Options
About this article
Cite this article as:
Legowska Anna, Debowski Dawid, Lukajtis Rafal, Sztabkowska Emilia, Mizeria Aneta, Brzozowski Krzysztof, Wysocka Magdalena, Lesner Adam and Rolka Krzysztof, Introduction of Pro and Its Analogues in the Conserved P1 Position of Trypsin Inhibitor SFTI-1 Retains Its Inhibitory Activity, Protein & Peptide Letters 2011; 18 (11) . https://dx.doi.org/10.2174/092986611797201002
DOI https://dx.doi.org/10.2174/092986611797201002 |
Print ISSN 0929-8665 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5305 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
The Screening of Renoprotective Agents by 99mTc-DMSA: A Review of Preclinical Studies
Current Radiopharmaceuticals Oxidative Stress and Endothelial Function: Therapeutic Interventions
Recent Patents on Cardiovascular Drug Discovery An Overview of Interleukin-1 Receptor Antagonist, Anakinra, in the Treatment of Cutaneous Diseases
Current Clinical Pharmacology Peripheral Chemo-Cytokine Profiles in Alzheimers and Parkinsons Diseases
Mini-Reviews in Medicinal Chemistry Development of Prolactin Receptor Antagonists: Same Goal, Different Ways
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery The Role of Autophagy in Rheumatic Disease
Current Drug Targets Combating Malaria with Plant Molecules: A Brief Update
Current Medicinal Chemistry Clinical and Forensic Signs Related to Opioids Abuse
Current Drug Abuse Reviews Neuropeptide Systems and Schizophrenia
CNS & Neurological Disorders - Drug Targets Gene Expression Profiling in Rodent Models for Schizophrenia
Current Neuropharmacology Quercetin and its Relative Therapeutic Potential Against COVID-19: A Retrospective Review and Prospective Overview
Current Molecular Medicine Emerging Influenza Viruses: Past and Present
Current Molecular Medicine Pharmacology of the Human Saphenous Vein
Current Vascular Pharmacology Editorial: Drug Targets and Biomarkers for Obstetric/Gynecologic/Reproductive Diseases
Current Drug Targets Congenital Solitary Functioning Kidney: A Review
Current Medicinal Chemistry A Novel Treatment Strategy for Sepsis and Septic Shock Based on the Interactions between Prostanoids, Nitric Oxide, and 20-Hydroxyeicosatetraenoic Acid
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Basic Sleep Mechanisms: An Integrative Review
Central Nervous System Agents in Medicinal Chemistry Design, Synthesis and Preliminary Evaluation of Novel Imperatorin Derivatives as Vasorelaxant Agents
Medicinal Chemistry Recombination Proteins and Telomere Stability in Plants
Current Protein & Peptide Science Antimicrobial Peptides: Mediators of Innate Immunity as Templates for the Development of Novel Anti-Infective and Immune Therapeutics
Current Pharmaceutical Design