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The 1,5-Disubstituted Tetrazole Ring as a cis-Amide Bond Surrogate
1Department of Molecular Biology and Pharmacology, Center for Molecular Design, Washington University, St. Louis, MO.
Methods in Molecular Medicine
|March 8, 2011
Summary
Proline and N-methyl amino acids, unique in forming N-alkyl amide bonds, exhibit cis-trans isomerism. This conformational property in peptides is linked to biological activity and receptor binding, influencing protein structure and function.
Area of Science:
- Biochemistry
- Structural Biology
- Peptide Chemistry
Background:
- Proline is unique among ribosomal amino acids, forming N-alkyl amide bonds.
- N-methyl amino acids are common in natural products and influence peptide conformation.
- Cis-trans isomerism of amide bonds is a key conformational characteristic.
Purpose of the Study:
- To explore the role of N-alkyl amide bond isomerism in peptides.
- To investigate the correlation between cis-isomer content and biological activity.
- To understand the structural implications of cis-amide bonds in protein function.
Main Methods:
- Nuclear Magnetic Resonance (NMR) spectroscopy to observe cis-trans isomerism.
- Analysis of peptide analogs like angiotensin and thyroliberin (TRH).
- Review of crystal structures and proposed roles in transmembrane proteins.
Main Results:
- Cis-trans isomerism is readily observed in proline and N-methyl amino acid peptides via NMR.
- Correlation found between cis-isomer quantity and biological activity in certain peptide analogs.
- Cis-amide bonds are occasionally observed in protein crystal structures and predispose peptides to reverse turns.
Conclusions:
- The cis-isomer of N-alkyl amide bonds may be responsible for biological activity by binding to receptors.
- Cis-amide bonds, particularly in proline residues, may play a role in protein structure and transmembrane signaling.
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