Solid phase reductive alkylation techniques in analogue peptide bond and sidechain modification
✍ Scribed by David H. Coy; Simon J. Hocart; Yusuke Sasaki
- Book ID
- 104203731
- Publisher
- Elsevier Science
- Year
- 1988
- Tongue
- French
- Weight
- 428 KB
- Volume
- 44
- Category
- Article
- ISSN
- 0040-4020
No coin nor oath required. For personal study only.
✦ Synopsis
The presence of a reduced peptide bond in a biologically active peptide usually has profound effects on conformation and potency. The CH2NH group may be a useful tool for delineating important hydrogen-bonding points and may also offer a general strategy for the production of enzyme resistance and potent competitive antagonists containing minimal structural alteration. The introduction of the group by solid phase reductive alkylation with a protected amino acid aldehyde offers a rapid route to peptides containing one or even many bond replacements. Potential racemization problems have been investigated and appear to be mostly related to the LiAIH4 reduction of amino acid dimethylhydroxamates to the aldehydes.
Conditions are presented which prevent this, however, prolonged storage of amino acid aldehydes does appear to result in substantial racemization. The stability of commonly used