Investigation of the structure-activity relationship at the N-terminal part of minigastrin analogs.

ABSTRACT:

Background

Over the last years, several strategies have been reported to improve the metabolic stability of minigastrin analogs. However, currently applied compounds still reveal limited in vitro and in vivo stability. We thus performed a glycine scan at the N-terminus of DOTA-MGS5 (DOTA-D-Glu-Ala-Tyr-Gly-Trp-(N-Me)Nle-Asp-1-Nal) to systematically analyze the peptide structure. We substituted N-terminal amino acids by simple PEG spacers and investigated in vitro stability in human serum. Furthermore, we evaluated different modifications on its tetrapeptide binding sequence (H-Trp-(N-Me)Nle-Asp-1-Nal-NH₂).

Results

Affinity data of all glycine scan peptides were found to be in a low nanomolar range (4.2-8.5 nM). However, a truncated compound lacking the D-γ-Glu-Ala-

SUBMITTER: Holzleitner N 

PROVIDER: S-EPMC10329608 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature