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Amino Acids

, Volume 46, Issue 1, pp 125–151 | Cite as

Incorporation of post-translational modified amino acids as an approach to increase both chemical and biological diversity of conotoxins and conopeptides

  • Michael J. Espiritu
  • Chino C. Cabalteja
  • Christopher K. Sugai
  • Jon-Paul BinghamEmail author
Review Article

Abstract

Bioactive peptides from Conus venom contain a natural abundance of post-translational modifications that affect their chemical diversity, structural stability, and neuroactive properties. These modifications have continually presented hurdles in their identification and characterization. Early endeavors in their analysis relied on classical biochemical techniques that have led to the progressive development and use of novel proteomic-based approaches. The critical importance of these post-translationally modified amino acids and their specific assignment cannot be understated, having impact on their folding, pharmacological selectivity, and potency. Such modifications at an amino acid level may also provide additional insight into the advancement of conopeptide drugs in the quest for precise pharmacological targeting. To achieve this end, a concerted effort between the classical and novel approaches is needed to completely elucidate the role of post-translational modifications in conopeptide structure and dynamics. This paper provides a reflection in the advancements observed in dealing with numerous and multiple post-translationally modified amino acids within conotoxins and conopeptides and provides a summary of the current techniques used in their identification.

Keywords

Conotoxins Conopeptides Post-translational modifications Peptide toxins Amino acids 

Abbreviations

Aph

4-Aminophenylalanine

Abu

α-Aminobutyric acid

Gla

γ-Carboxy glutamic acid

CRS

γ-Carboxylation recognition sequence

αα

Amino acid

CID

Collision-induced desorption

Da

Dalton

KD

Dissociation constant

ESI–MS

Electrospray ionization mass spectrometry

ER

Endoplasmic reticulum

LSI–MS

Laser spray ionization

MS

Mass spectrometry

MALDI–MS

Matrix assisted laser desorption ionization mass spectrometry

MALDI–TOF–MS

Matrix assisted laser desorption ionization time-of-flight mass spectrometry

nAChR

Nicotinic acetylcholine receptor

PPI

Peptidylprolyl isomerase

PFA

Performic acid

pKa

Logarithmic acid dissociation constant

PSD

Post-source decay

PTM

Post-translational modification

PDI

Protein disulfide isomerase

RP–HPLC

Reverse phase high performance liquid chromatography

SPPS

Solid phase peptide synthesis

TCEP

Tris(2-carboxyethyl) phosphine

XRC

X-ray crystallography

Notes

Acknowledgments

We wish to acknowledge the past and continued financial support from USDA TSTAR (# 2009-34135-20067) & HATCH (HAW00595-R)(J-P.B) which have helped expand our own horizons in understanding the importance of conotoxin/conopeptide post-translational modifications.

Conflict of interest

The authors state that there is no conflict of interest.

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Copyright information

© Springer-Verlag Wien 2013

Authors and Affiliations

  • Michael J. Espiritu
    • 1
  • Chino C. Cabalteja
    • 1
  • Christopher K. Sugai
    • 1
  • Jon-Paul Bingham
    • 1
    Email author
  1. 1.Department of Molecular Biosciences and Bioengineering, College of Tropical Agriculture and Human ResourcesUniversity of HawaiiHonoluluUSA

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