An Immune-Stimulatory Helix-Loop-Helix Peptide: Selective Inhibition of CTLA-4-B7 Interaction.
Amino Acid Sequence
B7-1 Antigen
/ metabolism
CTLA-4 Antigen
/ metabolism
Dendritic Cells
/ drug effects
Helix-Loop-Helix Motifs
Humans
Immunoglobulin Fc Fragments
/ metabolism
Immunologic Factors
/ chemical synthesis
Leukocytes, Mononuclear
/ drug effects
Lymphocyte Activation
/ drug effects
Peptide Library
Peptides
/ chemical synthesis
Protein Binding
/ drug effects
Saccharomyces cerevisiae
/ genetics
Journal
ACS chemical biology
ISSN: 1554-8937
Titre abrégé: ACS Chem Biol
Pays: United States
ID NLM: 101282906
Informations de publication
Date de publication:
21 02 2020
21 02 2020
Historique:
pubmed:
17
12
2019
medline:
10
2
2021
entrez:
17
12
2019
Statut:
ppublish
Résumé
Molecular-targeting peptides and mini-proteins are promising alternatives to antibodies in a wide range of applications in bioscience and medicine. We have developed a helix-loop-helix (HLH) peptide as an alternative to antibodies to inhibit specific protein interactions. Cytotoxic T lymphocyte antigen-4 (CTLA-4) downregulates immune responses of cytotoxic T-cells by interaction with B7-1, a co-stimulatory molecule expressed on antigen presenting cells (APCs). To induce immune stimulatory activity, we used directed evolution methods to generate a HLH peptide that binds to CTLA-4, inhibiting the CTLA-4-B7-1 interaction and inducing immune stimulatory activity. Yeast-displayed libraries of HLH peptides were constructed and screened against CTLA-4 and identified the binding peptide Y-2, which exhibits a moderate affinity. The affinity of Y-2 was improved by
Identifiants
pubmed: 31841301
doi: 10.1021/acschembio.9b00743
doi:
Substances chimiques
B7-1 Antigen
0
CTLA-4 Antigen
0
CTLA4 protein, human
0
Immunoglobulin Fc Fragments
0
Immunologic Factors
0
Peptide Library
0
Peptides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM