Modulation of Co-stimulatory Signal from CD2-CD58 Proteins by a Grafted Peptide

Overview

Journal Chem Biol Drug Des

Specialties Biochemistry
Pharmacology

Date 2020 Sep 18

PMID 32946175

Citations 4

Authors

Pravin Parajuli

Rushikesh Sable

Leeza Shrestha

Achyut Dahal

Ted Gauthier

Veena Taneja

Seetharama Jois

Affiliations

Soon will be listed here.

Abstract

Peptides were designed to inhibit the protein-protein interaction of CD2 and CD58 to modulate the immune response. This work involved the design and synthesis of eight different peptides by replacing each amino acid residue in peptide 6 with alanine as well as grafting the peptide to the sunflower trypsin-inhibitor framework. From the alanine scanning studies, mutation at position 2 of the peptide was shown to result in increased potency to inhibit cell adhesion interactions. The most potent peptide from the alanine scanning was further studied for its detailed three-dimensional structure and binding to CD58 protein using surface plasmon resonance and flow cytometry. This peptide was used to graft to the sunflower trypsin inhibitor to improve the stability of the peptide. The grafted peptide, SFTI-a1, was further studied for its potency as well as its thermal, chemical, and enzymatic stability. The grafted peptide exhibited improved activity compared to our previously grafted peptide and was stable against thermal and enzymatic degradation.

Citing Articles

Conformationally constrained cyclic grafted peptidomimetics targeting protein-protein interactions.

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Virtual Screening and Binding Analysis of Potential CD58 Inhibitors in Colorectal Cancer (CRC).

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Targeting protein-protein interaction for immunomodulation: A sunflower trypsin inhibitor analog peptidomimetic suppresses RA progression in CIA model.

Dahal A, Parajuli P, Singh S, Shrestha L, Sonju J, Shrestha P J Pharmacol Sci. 2022; 149(3):124-138.

PMID: 35641025 PMC: 9208026. DOI: 10.1016/j.jphs.2022.04.005.

Peptides and peptidomimetics as therapeutic agents for Covid-19.

Dahal A, Sonju J, Kousoulas K, Jois S Pept Sci (Hoboken). 2021; 114(1):e24245.

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