Synthesis and in vitro characterization of glycopeptide drug candidates related to pacap1–23

Christopher R. Apostol; Parthasaradhireddy Tanguturi; Lajos Z. Szabò; Daniel Varela; Thiago Gilmartin; John M. Streicher; Robin Polt

doi:10.3390/molecules26164932

Synthesis and in vitro characterization of glycopeptide drug candidates related to pacap_1–23

Christopher R. Apostol, Parthasaradhireddy Tanguturi, Lajos Z. Szabò, Daniel Varela, Thiago Gilmartin, John M. Streicher, Robin Polt

Research output: Contribution to journal › Article › peer-review

Abstract

The search for efficacious treatment of neurodegenerative and progressive neuroinflammatory diseases continues, as current therapies are unable to halt or reverse disease progression. PACAP represents one potential therapeutic that provides neuroprotection effects on neurons, and also modulates inflammatory responses and circulation within the brain. However, PACAP is a relatively long peptide hormone that is not trivial to synthesize. Based on previous observations that the shortened isoform PACAP_1–23 is capable of inducing neuroprotection in vitro, we were inspired to synthesize shortened glycopeptide analogues of PACAP_1–23 . Herein, we report the synthesis and in vitro characterization of glycosylated PACAP_1–23 analogues that interact strongly with the PAC1 and VPAC1 receptors, while showing reduced activity at the VPAC2 receptor.

Original language	English (US)
Article number	4932
Journal	Molecules
Volume	26
Issue number	16
DOIs	https://doi.org/10.3390/molecules26164932
State	Published - Aug 2 2021

Keywords

Alzheimer’s
Glycopeptide
Glycosylation
Parkinson’s
Stroke

ASJC Scopus subject areas

Analytical Chemistry
Chemistry (miscellaneous)
Molecular Medicine
Pharmaceutical Science
Drug Discovery
Physical and Theoretical Chemistry
Organic Chemistry

Access to Document

10.3390/molecules26164932

Cite this

@article{987b5b256c6a49e89a5d913f1953d102,

title = "Synthesis and in vitro characterization of glycopeptide drug candidates related to pacap1–23",

abstract = "The search for efficacious treatment of neurodegenerative and progressive neuroinflammatory diseases continues, as current therapies are unable to halt or reverse disease progression. PACAP represents one potential therapeutic that provides neuroprotection effects on neurons, and also modulates inflammatory responses and circulation within the brain. However, PACAP is a relatively long peptide hormone that is not trivial to synthesize. Based on previous observations that the shortened isoform PACAP1–23 is capable of inducing neuroprotection in vitro, we were inspired to synthesize shortened glycopeptide analogues of PACAP1–23 . Herein, we report the synthesis and in vitro characterization of glycosylated PACAP1–23 analogues that interact strongly with the PAC1 and VPAC1 receptors, while showing reduced activity at the VPAC2 receptor.",

keywords = "Alzheimer{\textquoteright}s, Glycopeptide, Glycosylation, Parkinson{\textquoteright}s, Stroke",

author = "Apostol, {Christopher R.} and Parthasaradhireddy Tanguturi and Szab{\`o}, {Lajos Z.} and Daniel Varela and Thiago Gilmartin and Streicher, {John M.} and Robin Polt",

note = "Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = aug,

day = "2",

doi = "10.3390/molecules26164932",

language = "English (US)",

volume = "26",

journal = "Molecules",

issn = "1420-3049",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "16",

}

TY - JOUR

T1 - Synthesis and in vitro characterization of glycopeptide drug candidates related to pacap1–23

AU - Apostol, Christopher R.

AU - Tanguturi, Parthasaradhireddy

AU - Szabò, Lajos Z.

AU - Varela, Daniel

AU - Gilmartin, Thiago

AU - Streicher, John M.

AU - Polt, Robin

PY - 2021/8/2

Y1 - 2021/8/2

N2 - The search for efficacious treatment of neurodegenerative and progressive neuroinflammatory diseases continues, as current therapies are unable to halt or reverse disease progression. PACAP represents one potential therapeutic that provides neuroprotection effects on neurons, and also modulates inflammatory responses and circulation within the brain. However, PACAP is a relatively long peptide hormone that is not trivial to synthesize. Based on previous observations that the shortened isoform PACAP1–23 is capable of inducing neuroprotection in vitro, we were inspired to synthesize shortened glycopeptide analogues of PACAP1–23 . Herein, we report the synthesis and in vitro characterization of glycosylated PACAP1–23 analogues that interact strongly with the PAC1 and VPAC1 receptors, while showing reduced activity at the VPAC2 receptor.

AB - The search for efficacious treatment of neurodegenerative and progressive neuroinflammatory diseases continues, as current therapies are unable to halt or reverse disease progression. PACAP represents one potential therapeutic that provides neuroprotection effects on neurons, and also modulates inflammatory responses and circulation within the brain. However, PACAP is a relatively long peptide hormone that is not trivial to synthesize. Based on previous observations that the shortened isoform PACAP1–23 is capable of inducing neuroprotection in vitro, we were inspired to synthesize shortened glycopeptide analogues of PACAP1–23 . Herein, we report the synthesis and in vitro characterization of glycosylated PACAP1–23 analogues that interact strongly with the PAC1 and VPAC1 receptors, while showing reduced activity at the VPAC2 receptor.

KW - Alzheimer’s

KW - Glycopeptide

KW - Glycosylation

KW - Parkinson’s

KW - Stroke

UR - http://www.scopus.com/inward/record.url?scp=85113738389&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85113738389&partnerID=8YFLogxK

U2 - 10.3390/molecules26164932

DO - 10.3390/molecules26164932

M3 - Article

C2 - 34443519

AN - SCOPUS:85113738389

SN - 1420-3049

VL - 26

JO - Molecules

JF - Molecules

IS - 16

M1 - 4932

ER -