Work

Re-evaluation of Cyclic Peptide Binding to Neurotensin Receptor 1 by Shifting the Peptide Register during Synthesis

Year: 2024

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide The head-to-tail cyclic peptide cyclo [Arg-Lys-Pro-Tyr-Tle-Leu] (peptide 1, where Tle is l - tert -Leu) has previously been reported to bind to neurotensin receptor 1 (NTS1) (pKi = 5.97). Upon seeking to reproduce this finding, we found that peptide 1 did not have a measurable affinity for NTS1. However, a semipurified preparation of peptide 1 appeared to bind to NTS1 with pKi = 5.83 ± 0.25 SEM. Resynthesis of peptide 1 using a shifted peptide register gave linear and cyclic forms of peptide 1 that were both unable to bind to NTS1. We observe that the previously reported activity of peptide 1 may be due to the presence of high affinity linear contaminants. Approximately 3% contamination with the linear variant would explain the apparent binding of the semipure peptide 1 sample. From this study, we propose that shifting the peptide register during synthesis as a strategy to minimize the presence of potent precursor contaminants.

Source: ACS Medicinal Chemistry Letters

DOI: 10.1021/acsmedchemlett.4c00542

Authors: Lazarus Andrew de Zhang, Mengjie Liu, Daniel J. Scott, David K. Chalmers

Institutions: The University of Melbourne, Florey Institute of Neuroscience and Mental Health, Monash University

Language: English

Topic: Chemical Synthesis and Analysis

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $4,500

Funder: National Health and Medical Research Council