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Related Experiment Videos

Ethanol antagonist peptides: structural specificity without stereospecificity.

Michael F Wilkemeyer1, Shao-Yu Chen, Carrie E Menkari

  • 1Neurology Service for Veterans Affairs Boston Healthcare System, 1400 VFW Parkway, West Roxbury, MA 02132, USA.

The Journal of Pharmacology and Experimental Therapeutics
|February 6, 2004
PubMed
Summary

Ethanol harms developing nervous systems by disrupting L1 cell adhesion. Novel d-peptides, like d-NAP, show potent ethanol antagonism without stereospecificity, offering potential fetal alcohol syndrome prevention.

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Pharmacology

Background:

  • Ethanol exposure during development can lead to neurotoxicity.
  • The L1 cell adhesion molecule is implicated in ethanol's detrimental effects on the developing nervous system.
  • Specific small peptides, NAPVSIPQ (NAP) and SALLRSIPA (SAL), have shown potential as ethanol antagonists.

Purpose of the Study:

  • To investigate the stereospecificity of NAP and SAL as ethanol antagonists.
  • To explore the structure-activity relationships of these peptides.
  • To evaluate the efficacy of d-NAP in preventing ethanol-induced embryotoxicity.

Main Methods:

  • Utilized NIH/3T3 cells transfected with human L1 and NG108-15 neural cells.
  • Tested d-NAP and its derivatives for ethanol antagonist activity.

Related Experiment Videos

  • Employed mouse whole embryo culture to assess growth retardation.

    • Main Results:

    • NAP and SAL exhibit potent ethanol antagonism at extremely low concentrations (femtomolar to picomolar).
    • Both d-NAP and l-NAP demonstrate a lack of stereospecificity in their ethanol antagonist activity.
    • The Ser-Ile-Pro motif, particularly the Ile residue, is crucial for the activity of d-NAP, l-NAP, and l-SAL.
    • d-NAP effectively mitigated ethanol-induced growth retardation in mouse whole embryo culture.

    Conclusions:

    • The ethanol antagonist activity of NAP and SAL is not stereospecific.
    • d-NAP is a potent ethanol antagonist and may be more resistant to proteases.
    • d-NAP presents a promising therapeutic avenue for preventing fetal alcohol syndrome.