Design, Synthesis and Structure of Peptides

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (15 April 2022) | Viewed by 8519

Special Issue Editors


E-Mail Website
Guest Editor
Laboratory of Chemical Biology, Institute of Biochemistry, Biological Research Centre, Szeged, Hungary
Interests: structure-activity relationships of biomolecules

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Guest Editor
Université de Paris, BFA, UMR 8251, CNRS, ERL U1133, Inserm, F-75013 Paris, France
Interests: structural bioinformatics; peptide-protein interactions; protein-protein interactions; peptide design; protein structure analysis and modeling

Special Issue Information

Dear Colleagues,

The introduction of solid-phase peptide synthesis nearly two generations ago, augmented with mild auxiliary chemical procedures, has made synthetic peptides easily and widely accessible. In the following decades, synthetic peptides have drawn remarkable attention involving diverse scientific fields. Peptide chains are assembled in a simple modular fashion yet may possess an exceptionally high degree of chemical diversity. As a result, synthetic peptides have found a wide variety of applications. Beyond the classical use as model systems for study of the protein folding problem, synthetic peptides are now to be found in more application-oriented fields, such as the design of foldamers, biomaterials, drug delivery systems, and tissue regeneration scaffolds, to name but a few. Naturally occurring peptide hormones and host defense systems serve as useful templates for the development of novel agents targeting various diseases and medical conditions, such as chronic pain, cancer, microbial infection, and obesity. The increasing diversity of such potential applications has posed new challenges to the design, synthesis, and structural analysis of peptides and peptidomimetics.

Scientists working in the broad field of peptides are invited to submit original research and review articles reporting on new synthetic approaches or solutions, characterization of unique structures or novel structural assemblies, and the design of peptides or peptidomimetics which address pharmacological obstacles of therapeutic application.

Dr. Attila Borics
Dr. Pierre Tuffery
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • peptides
  • peptidomimetics
  • peptide assemblies
  • peptide foldamers
  • biomaterials
  • drug development
  • peptide design
  • peptide synthesis
  • structural characterization

Published Papers (2 papers)

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Research

16 pages, 2369 KiB  
Article
Development of High Affinity Calcitonin Analog Fragments Targeting Extracellular Domains of Calcitonin Family Receptors
by Sangmin Lee
Biomolecules 2021, 11(9), 1364; https://doi.org/10.3390/biom11091364 - 15 Sep 2021
Cited by 2 | Viewed by 2533
Abstract
The calcitonin and amylin receptors (CTR and AMY receptors) are the drug targets for osteoporosis and diabetes treatment, respectively. Salmon calcitonin (sCT) and pramlintide were developed as peptide drugs that activate these receptors. However, next-generation drugs with improved receptor binding profiles are desirable [...] Read more.
The calcitonin and amylin receptors (CTR and AMY receptors) are the drug targets for osteoporosis and diabetes treatment, respectively. Salmon calcitonin (sCT) and pramlintide were developed as peptide drugs that activate these receptors. However, next-generation drugs with improved receptor binding profiles are desirable for more effective pharmacotherapy. The extracellular domain (ECD) of CTR was reported as the critical binding site for the C-terminal half of sCT. For the screening of high-affinity sCT analog fragments, purified CTR ECD was used for fluorescence polarization/anisotropy peptide binding assay. When three mutations (N26D, S29P, and P32HYP) were introduced to the sCT(22–32) fragment, sCT(22–32) affinity for the CTR ECD was increased by 21-fold. CTR was reported to form a complex with receptor activity-modifying protein (RAMP), and the CTR:RAMP complexes function as amylin receptors with increased binding for the peptide hormone amylin. All three types of functional AMY receptor ECDs were prepared and tested for the binding of the mutated sCT(22–32). Interestingly, the mutated sCT(22–32) also retained its high affinity for all three types of the AMY receptor ECDs. In summary, the mutated sCT(22–32) showing high affinity for CTR and AMY receptor ECDs could be considered for developing the next-generation peptide agonists. Full article
(This article belongs to the Special Issue Design, Synthesis and Structure of Peptides)
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14 pages, 14169 KiB  
Article
Discovery of Novel Allosteric Modulators Targeting an Extra-Helical Binding Site of GLP-1R Using Structure- and Ligand-Based Virtual Screening
by Qingtong Zhou, Wanjing Guo, Antao Dai, Xiaoqing Cai, Márton Vass, Chris de Graaf, Wenqing Shui, Suwen Zhao, Dehua Yang and Ming-Wei Wang
Biomolecules 2021, 11(7), 929; https://doi.org/10.3390/biom11070929 - 23 Jun 2021
Cited by 7 | Viewed by 5362
Abstract
Allosteric modulators have emerged with many potential pharmacological advantages as they do not compete the binding of agonist or antagonist to the orthosteric sites but ultimately affect downstream signaling. To identify allosteric modulators targeting an extra-helical binding site of the glucagon-like peptide-1 receptor [...] Read more.
Allosteric modulators have emerged with many potential pharmacological advantages as they do not compete the binding of agonist or antagonist to the orthosteric sites but ultimately affect downstream signaling. To identify allosteric modulators targeting an extra-helical binding site of the glucagon-like peptide-1 receptor (GLP-1R) within the membrane environment, the following two computational approaches were applied: structure-based virtual screening with consideration of lipid contacts and ligand-based virtual screening with the maintenance of specific allosteric pocket residue interactions. Verified by radiolabeled ligand binding and cAMP accumulation experiments, two negative allosteric modulators and seven positive allosteric modulators were discovered using structure-based and ligand-based virtual screening methods, respectively. The computational approach presented here could possibly be used to discover allosteric modulators of other G protein-coupled receptors. Full article
(This article belongs to the Special Issue Design, Synthesis and Structure of Peptides)
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