AI Article Synopsis
- The study explores how modifying the N-terminal amino acids of peptide analogues with Cys-Asp or Cys impacts their ability to inhibit the VEGF-A/Neuropilin-1 complex.
- The introduction of a Cys residue resulted in a significant 100-fold decrease in the IC value, indicating increased potency compared to the original peptides.
- The research highlights that adding Cys at the N-terminus consistently enhances the inhibitory effectiveness of various potent NRP-1 peptide ligands, particularly enhancing the affinity of the tetrapeptide KPRR by extending the CendR motif with a Cys.
Article Abstract
The structure-activity relationship of branched H-Lys(Arg)-Dab-Dhp-Arg-OH sequence analogues, modified with Cys-Asp or Cys at N-terminal amino acids (Lys, Arg), in VEGF-A/Neuropilin-1 complex inhibition is presented. The addition of Cys residue led to a 100-fold decrease in the IC value, compared to the parent peptide. The change occurred regardless of coupling Cys to the free N-terminal amino group present in the main or the side chain. A few analogues extended by the attachment of Cys at the N-terminus of several potent NRP-1 peptide ligands documented in the literature are also presented. In all studied cases, the enhancement of inhibitory properties after the addition of Cys at the N-terminus is observed. It is particularly evident for the tetrapeptide derived from the C-terminus of VEGF-A (KPRR), suggesting that extending the K/RXXK/R motif (CendR) with the Cys moiety can significantly improve affinity to NRP-1 of CendR peptides.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175122 | PMC |
| http://dx.doi.org/10.3390/biom10030448 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Targeted deletion of the pancreatic β-cell oxytocin receptor and its effects on metabolic regulation and β-cell health.
Front Endocrinol (Lausanne)
January 2025
Department of Psychology, University of Miami, Coral Gables, FL, United States.
The neuropeptide oxytocin (OXT) and its receptor (OXTR) have been shown to play an important role in glucose metabolism, and pancreatic islets express this ligand and receptor. In the current study, OXTR expression was identified in α-, β-, and δ-cells of the pancreatic islet by RNA hybridization, and OXT protein expression was observed only in β-cells. In order to examine the contribution of islet OXT/OXTR in glycemic control and islet β-cell heath, we developed a β-cell specific OXTR knock-out (β-KO) mouse.
View Article and Find Full Text PDFShort linear peptide motifs play important roles in cell signaling. They can act as modification sites for enzymes and as recognition sites for peptide binding domains. SH2 domains bind specifically to tyrosine-phosphorylated proteins, with the affinity of the interaction depending strongly on the flanking sequence.
View Article and Find Full Text PDFMHC-I proteins present epitopic peptides to CD8+ T cells to elicit multifaceted adaptive immune responses. The affinity and avidity of interactions between peptide-MHC molecules and T-cell receptors (TCR) are fundamental parameters that contribute to the induction of activated or anergic T cell states. Here, we present a loadable system, VLP-Open HLA, featuring a virus-like particle (VLP) that can accommodate up to 60 loadable HLA (HLA - human leukocyte antigen) molecules.
View Article and Find Full Text PDFTauopathies, a group of neurodegenerative disorders, are characterized by the abnormal aggregation of tau proteins into neurofibrillary tangles (NFTs), driving synaptic dysfunction, neuronal loss, and disease progression through tau aggregate propagation. Graphene quantum dots (GQDs) functionalized with - cysteine ( -GQDs) have shown promise in inhibiting tau aggregation and transmission π-π stacking and electrostatic interactions with tau proteins. However, the non-specific binding of GQDs to various proteins in the physiological environment, such as serum albumin, limits their clinical translation.
View Article and Find Full Text PDFExpression and purification of an activated Orexin receptor 1- G-protein complex.
Protein Expr Purif
January 2025
VIB-VUB Center for Structural Biology, VIB, Pleinlaan 2, Brussels, Belgium; Structural Biology Brussels, Vrije Universiteit Brussel (VUB), Pleinlaan 2, Brussels, Belgium. Electronic address:
Orexin receptors constitute a family of class A G-protein coupled receptors. There are two subtypes of orexin receptors, namely OX1R and OX2R. OX1R and OX2R are widely distributed in the central nervous system and are the targets for the peptide neurotransmitters orexin-A and orexin-B.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!