Heparin Oligosaccharides as Vasoactive Intestinal Peptide Inhibitors via their Binding Process Characterization.

ELISA assay Heparin oligosaccharides Interaction Isothermal titration calorimetry Vasoactive intestinal peptide cAMP

Journal

Current protein & peptide science
ISSN: 1875-5550
Titre abrégé: Curr Protein Pept Sci
Pays: United Arab Emirates
ID NLM: 100960529

Informations de publication

Date de publication:
26 Jan 2024
Historique:
received: 09 11 2023
revised: 02 01 2024
accepted: 12 01 2024
medline: 29 1 2024
pubmed: 29 1 2024
entrez: 29 1 2024
Statut: aheadofprint

Résumé

It has been proven that vasoactive intestinal peptide (VIP) was involved in the pathogenesis of prostate cancer. Cardin et al. found that by an alanine scan, the heparin-binding site on VIP was exactly the same sequence in VIP and its receptor. Therefore, heparin could competitively block the binding of VIP and its receptor. However, the structure-activity relationship between heparin and VIP has not been reported, especially in terms of the sequence and sulfation patterns of heparin oligosaccharides upon binding to VIP. The binding process between heparin oligosaccharides and VIPA variety of experiments was designed to study the structure-activity relationship between heparin oligosaccharides and VIP. Heparin was enzymatically digested and purified to produce heparin oligosaccharides, and the structures were characterized by NMR. The binding capacity between heparin oligosaccharides and VIP was analyzed by GMSA and ITC experiments. The binding between heparin oligosaccharides and VIP was simulated using a molecular docking program to show the complex. ELISA assay was used to investigate the effect of non-anticoagulant heparin oligosaccharides on the VIP-mediated cAMP/PKA signaling pathway in vitro. The results indicated that both the length and the sulfation pattern of heparin oligosaccharides affected its binding to VIP. VIP could induce the expression of cAMP at a higher level in PC3 cells, which could be regulated by the interaction of heparin oligosaccharides and VIP. The binding between heparin oligosaccharides and VIP could block the binding between VIP and its receptor on tumor cells. Downloading the regulation of the expression level of cAMP could possibly further affect the subsequent activation of PKA. These non-anticoagulant heparin oligosaccharides may block the VIP-mediated cAMP/PKA signaling pathway and thus exert their antitumor activity.

Sections du résumé

BACKGROUND BACKGROUND
It has been proven that vasoactive intestinal peptide (VIP) was involved in the pathogenesis of prostate cancer. Cardin et al. found that by an alanine scan, the heparin-binding site on VIP was exactly the same sequence in VIP and its receptor. Therefore, heparin could competitively block the binding of VIP and its receptor. However, the structure-activity relationship between heparin and VIP has not been reported, especially in terms of the sequence and sulfation patterns of heparin oligosaccharides upon binding to VIP.
OBJECTIVE OBJECTIVE
The binding process between heparin oligosaccharides and VIPA variety of experiments was designed to study the structure-activity relationship between heparin oligosaccharides and VIP.
METHODS METHODS
Heparin was enzymatically digested and purified to produce heparin oligosaccharides, and the structures were characterized by NMR. The binding capacity between heparin oligosaccharides and VIP was analyzed by GMSA and ITC experiments. The binding between heparin oligosaccharides and VIP was simulated using a molecular docking program to show the complex. ELISA assay was used to investigate the effect of non-anticoagulant heparin oligosaccharides on the VIP-mediated cAMP/PKA signaling pathway in vitro.
RESULTS RESULTS
The results indicated that both the length and the sulfation pattern of heparin oligosaccharides affected its binding to VIP. VIP could induce the expression of cAMP at a higher level in PC3 cells, which could be regulated by the interaction of heparin oligosaccharides and VIP.
CONCLUSION CONCLUSIONS
The binding between heparin oligosaccharides and VIP could block the binding between VIP and its receptor on tumor cells. Downloading the regulation of the expression level of cAMP could possibly further affect the subsequent activation of PKA. These non-anticoagulant heparin oligosaccharides may block the VIP-mediated cAMP/PKA signaling pathway and thus exert their antitumor activity.

Identifiants

DOI: 10.2174/0113892037287189240122110819 PMID: 38284716
pubmed: 38284716
pii: CPPS-EPUB-138039
doi: 10.2174/0113892037287189240122110819
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

Auteurs

Meixin Li (M)

National Glycoengineering Research Center, NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-based Medicine, Shandong University, Qingdao, Shandong, 266237, China.

Yaqi Xue (Y)

National Glycoengineering Research Center, NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-based Medicine, Shandong University, Qingdao, Shandong, 266237, China.

Lianli Chi (L)

National Glycoengineering Research Center, NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-based Medicine, Shandong University, Qingdao, Shandong, 266237, China.

Lan Jin (L)

National Glycoengineering Research Center, NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-based Medicine, Shandong University, Qingdao, Shandong, 266237, China.

Classifications MeSH