Modulation of co-stimulatory signal from CD2-CD58 proteins by a grafted peptide.
Amino Acid Sequence
Binding Sites
Binding, Competitive
CD2 Antigens
/ chemistry
CD58 Antigens
/ chemistry
Cell Adhesion
/ drug effects
Cell Line
Drug Design
Humans
Molecular Docking Simulation
Peptides, Cyclic
/ chemistry
Protein Binding
Protein Interaction Maps
/ drug effects
Protein Stability
T-Lymphocytes
/ cytology
Trypsin Inhibitors
/ pharmacology
CD2
CD58
alanine scanning
cell adhesion
immunomodulation
protein-protein interaction
Journal
Chemical biology & drug design
ISSN: 1747-0285
Titre abrégé: Chem Biol Drug Des
Pays: England
ID NLM: 101262549
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
01
08
2019
revised:
23
06
2020
accepted:
09
09
2020
pubmed:
19
9
2020
medline:
23
9
2021
entrez:
18
9
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32946175
doi: 10.1111/cbdd.13797
pmc: PMC8717467
mid: NIHMS1764637
doi:
Substances chimiques
CD2 Antigens
0
CD58 Antigens
0
Peptides, Cyclic
0
Trypsin Inhibitors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
607-627Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM103424
Pays : United States
Informations de copyright
© 2020 John Wiley & Sons A/S.
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