Neuropeptide-processing enzymes: Applications for drug discovery

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Neuropeptides serve many important roles in communication between cells and are an attractive target for drug discovery. Neuropeptides are produced from precursor proteins by selective cleavages at specific sites, and are then broken down by further cleavages. In general, the biosynthetic cleavages occur within the cell and the degradative cleavages occur postsecretion, although there are exceptions where intracellular processing leads to inactivation, or extracellular processing leads to activation of a particular neuropeptide. A relatively small number of peptidases are responsible for processing the majority of neuropeptides, both inside and outside of the cell. Thus, inhibition of any one enzyme will lead to a broad effect on several different neuropeptides and this makes it unlikely that such inhibitors would be useful therapeutics. However, studies with mutant animals that lack functional peptide-processing enzymes have facilitated the discovery of novel neuropeptides, many of which may be appropriate targets for therapeutics.

Original languageEnglish (US)
Article number44
JournalAAPS Journal
Volume7
Issue number2
DOIs
StatePublished - Oct 5 2005

Fingerprint

Drug Discovery
Neuropeptides
Enzymes
Protein Precursors
Cell Communication
Peptide Hydrolases
Peptides
Therapeutics

Keywords

  • Carboxypeptidase
  • Peptide biosynthesis
  • Peptidomics
  • Prohormone convertase

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Neuropeptide-processing enzymes : Applications for drug discovery. / Fricker, Lloyd D.

In: AAPS Journal, Vol. 7, No. 2, 44, 05.10.2005.

Research output: Contribution to journalArticle

@article{5c06939cdab946f6976a4d0158552577,
title = "Neuropeptide-processing enzymes: Applications for drug discovery",
abstract = "Neuropeptides serve many important roles in communication between cells and are an attractive target for drug discovery. Neuropeptides are produced from precursor proteins by selective cleavages at specific sites, and are then broken down by further cleavages. In general, the biosynthetic cleavages occur within the cell and the degradative cleavages occur postsecretion, although there are exceptions where intracellular processing leads to inactivation, or extracellular processing leads to activation of a particular neuropeptide. A relatively small number of peptidases are responsible for processing the majority of neuropeptides, both inside and outside of the cell. Thus, inhibition of any one enzyme will lead to a broad effect on several different neuropeptides and this makes it unlikely that such inhibitors would be useful therapeutics. However, studies with mutant animals that lack functional peptide-processing enzymes have facilitated the discovery of novel neuropeptides, many of which may be appropriate targets for therapeutics.",
keywords = "Carboxypeptidase, Peptide biosynthesis, Peptidomics, Prohormone convertase",
author = "Fricker, {Lloyd D.}",
year = "2005",
month = "10",
day = "5",
doi = "10.1208/aapsj070244",
language = "English (US)",
volume = "7",
journal = "AAPS Journal",
issn = "1522-1059",
publisher = "Springer New York",
number = "2",

}

TY - JOUR

T1 - Neuropeptide-processing enzymes

T2 - Applications for drug discovery

AU - Fricker, Lloyd D.

PY - 2005/10/5

Y1 - 2005/10/5

N2 - Neuropeptides serve many important roles in communication between cells and are an attractive target for drug discovery. Neuropeptides are produced from precursor proteins by selective cleavages at specific sites, and are then broken down by further cleavages. In general, the biosynthetic cleavages occur within the cell and the degradative cleavages occur postsecretion, although there are exceptions where intracellular processing leads to inactivation, or extracellular processing leads to activation of a particular neuropeptide. A relatively small number of peptidases are responsible for processing the majority of neuropeptides, both inside and outside of the cell. Thus, inhibition of any one enzyme will lead to a broad effect on several different neuropeptides and this makes it unlikely that such inhibitors would be useful therapeutics. However, studies with mutant animals that lack functional peptide-processing enzymes have facilitated the discovery of novel neuropeptides, many of which may be appropriate targets for therapeutics.

AB - Neuropeptides serve many important roles in communication between cells and are an attractive target for drug discovery. Neuropeptides are produced from precursor proteins by selective cleavages at specific sites, and are then broken down by further cleavages. In general, the biosynthetic cleavages occur within the cell and the degradative cleavages occur postsecretion, although there are exceptions where intracellular processing leads to inactivation, or extracellular processing leads to activation of a particular neuropeptide. A relatively small number of peptidases are responsible for processing the majority of neuropeptides, both inside and outside of the cell. Thus, inhibition of any one enzyme will lead to a broad effect on several different neuropeptides and this makes it unlikely that such inhibitors would be useful therapeutics. However, studies with mutant animals that lack functional peptide-processing enzymes have facilitated the discovery of novel neuropeptides, many of which may be appropriate targets for therapeutics.

KW - Carboxypeptidase

KW - Peptide biosynthesis

KW - Peptidomics

KW - Prohormone convertase

UR - http://www.scopus.com/inward/record.url?scp=30444432702&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=30444432702&partnerID=8YFLogxK

U2 - 10.1208/aapsj070244

DO - 10.1208/aapsj070244

M3 - Article

C2 - 16353923

AN - SCOPUS:30444432702

VL - 7

JO - AAPS Journal

JF - AAPS Journal

SN - 1522-1059

IS - 2

M1 - 44

ER -