TY - JOUR
T1 - Alkylating Angiotensin II Analogues
T2 - Synthesis, Analysis, and Biological Activity of Angiotensin II Analogues Containing the Nitrogen Mustard Melphalan in Position 8
AU - Hsieh, Kun hwa
AU - Marshall, Garland R.
PY - 1981/11
Y1 - 1981/11
N2 - Melphalan derivatives suitable for peptide synthesis, i.e., Boc-Mel and Mel-OBzl.HCl, have been prepared, and the integrity of their nitrogen mustard alkylating groups was examined by NMR, Volhard chlorine analysis, and colorimetric assay with 4-(p-nitrobenzyl)pyridine. By using the sensitive colorimetric assay, the stability of melphalan toward conditions commonly used for peptide synthesis, purification, and bioassay was evaluated. Further qualitative and quantitative assessment of the integrity of nitrogen mustard groups in angiotensin II was attempted in order to evaluate the significance of the observed biological results. [Ac-Asn1,Mel8]angiotensin II was a potent competitive antagonist of angiotensin II in vitro (rat uterus) but a transient and reversible inhibitor in vivo.
AB - Melphalan derivatives suitable for peptide synthesis, i.e., Boc-Mel and Mel-OBzl.HCl, have been prepared, and the integrity of their nitrogen mustard alkylating groups was examined by NMR, Volhard chlorine analysis, and colorimetric assay with 4-(p-nitrobenzyl)pyridine. By using the sensitive colorimetric assay, the stability of melphalan toward conditions commonly used for peptide synthesis, purification, and bioassay was evaluated. Further qualitative and quantitative assessment of the integrity of nitrogen mustard groups in angiotensin II was attempted in order to evaluate the significance of the observed biological results. [Ac-Asn1,Mel8]angiotensin II was a potent competitive antagonist of angiotensin II in vitro (rat uterus) but a transient and reversible inhibitor in vivo.
UR - http://www.scopus.com/inward/record.url?scp=0019847596&partnerID=8YFLogxK
U2 - 10.1021/jm00143a009
DO - 10.1021/jm00143a009
M3 - Article
C2 - 7310805
AN - SCOPUS:0019847596
SN - 0022-2623
VL - 24
SP - 1304
EP - 1310
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 11
ER -