Analysis of D-amino acid-containing neuropeptides in mollusks and rodents
type: CreativeWork
description: Modern mass spectrometry (MS)-based neuropeptidomics continues to reveal an unprecedented level of chemical complexity in the nervous system on the peptide level, with sometimes hundreds of peptides expressed by or secreted onto specific structures. These neuropeptides have evolved for animal behaviors and regulating neuronal circuits. Neuropeptides exert their responses through GPCRs in most cases, and in order to interact with the GPCR, their structure is important. Their structures are not solely defined by their peptide sequence, but may instead depend on the myriad post-translational modifications (PTMs) they undergo. Thus, the hunt for neuropeptides must include the discovery of the exact chemical forms of the physiologically active peptides as these are required to achieve their receptor binding capability, degradation and uptake pathways, and hence bioactivity. Life, on a molecular level, has a stereoselective preference for many biochemical processes. This is especially true for protein-derived neuropeptides, which are translated by ribosomes using exclusively L-amino acids. However, D-amino acids are present in animal peptides, first evidenced by dermorphin, an analgesic skin peptide in Phyllomedusa sauvagei. Dermorphin’s existence as a D-amino acid-containing peptide (DAACP) proved not to be a singularity, but instead revealed a novel post-translational modification: peptide isomerization. Roughly 40 endogenous animal DAACPs have been found in 3 evolutionarily distinct phyla as toxins, hormones, and importantly for this work, neuropeptides. Isomerization alters the three-dimensional shape of a peptide. This change in shape has been associated with a change in bioactivity of a peptide, with the DAACP being the sole bioactive form. However, isomerization does not change the molecular weight of a peptide, making it difficult to detect using MS. Thus, bioactive peptides are likely hiding in neuropeptidomics study under the assumption that these peptides, like…
abstract: Modern mass spectrometry (MS)-based neuropeptidomics continues to reveal an unprecedented level of chemical complexity in the nervous system on the peptide level, with sometimes hundreds of peptides expressed by or secreted onto specific structures. These neuropeptides have evolved for animal behaviors and regulating neuronal circuits. Neuropeptides exert their responses through GPCRs in most cases, and in order to interact with the GPCR, their structure is important. Their structures are not solely defined by their peptide sequence, but may instead depend on the myriad post-translational modifications (PTMs) they undergo. Thus, the hunt for neuropeptides must include the discovery of the exact chemical forms of the physiologically active peptides as these are required to achieve their receptor binding capability, degradation and uptake pathways, and hence bioactivity. Life, on a molecular level, has a stereoselective preference for many biochemical processes. This is especially true for protein-derived neuropeptides, which are translated by ribosomes using exclusively L-amino acids. However, D-amino acids are present in animal peptides, first evidenced by dermorphin, an analgesic skin peptide in Phyllomedusa sauvagei. Dermorphin’s existence as a D-amino acid-containing peptide (DAACP) proved not to be a singularity, but instead revealed a novel post-translational modification: peptide isomerization. Roughly 40 endogenous animal DAACPs have been found in 3 evolutionarily distinct phyla as toxins, hormones, and importantly for this work, neuropeptides. Isomerization alters the three-dimensional shape of a peptide. This change in shape has been associated with a change in bioactivity of a peptide, with the DAACP being the sole bioactive form. However, isomerization does not change the molecular weight of a peptide, making it difficult to detect using MS. Thus, bioactive peptides are likely hiding in neuropeptidomics study under the assumption that these peptides, like…
author: Livnat, Itamar
language: en
keywords: Neurochemistry, D-amino acid-containing peptides, Neuropeptides, Mass spectrometry (MS), Liquid chromatography, Aplysia californica, Liquid chromatography–mass spectrometry (LC-MS), Liquid chromatography–mass spectrometry/mass spectrometry (LC-MS/MS)
date published: 2017-08-10T20:32:41Z
date modified: 2026-07-22T22:24:34Z
provider: University of Illinois - Urbana-Champaign
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Illinois at Urbana-Champaign

PropertyValue
property ID: Handle
value: http://hdl.handle.net/2142/97668