TY - JOUR
T1 - Novel biologically active nonpeptidic inhibitors of myristoylCoArprotein NMyristoyltransferase
AU - Devadas, Balekudru
AU - Freeman, Sandra K.
AU - McWherter, Charles A.
AU - Kishore, Nandini S.
AU - Lodge, Jennifer K.
AU - Jackson-Machelski, Emily
AU - Gordon, Jeffrey I.
AU - Sikorski, James A.
PY - 1998/3/12
Y1 - 1998/3/12
N2 - A new class of biologically active nonpeptidic inhibitors of Candida albicans NMT has been synthesized starting from the octapeptide ALYASKLS-NH2 (2). The synthetic strategy entailed the preparation of novel protected Ser-Lys mimics 9 and 12 from (S)- or CR)-3-iodotyrosine and then grafting key enzyme recognition elements in a stepwise manner. Like 2, compounds 16, 17, and 18 are competitive Candida NMT inhibitors that bind to the peptide recognition site of the enzyme. Moreover, 16-18 have an affinity comparable to that of 2 even though they are devoid of peptide bonds. In contrast to 2, these nonpeptidic inhibitors exhibit antifungal activity.
AB - A new class of biologically active nonpeptidic inhibitors of Candida albicans NMT has been synthesized starting from the octapeptide ALYASKLS-NH2 (2). The synthetic strategy entailed the preparation of novel protected Ser-Lys mimics 9 and 12 from (S)- or CR)-3-iodotyrosine and then grafting key enzyme recognition elements in a stepwise manner. Like 2, compounds 16, 17, and 18 are competitive Candida NMT inhibitors that bind to the peptide recognition site of the enzyme. Moreover, 16-18 have an affinity comparable to that of 2 even though they are devoid of peptide bonds. In contrast to 2, these nonpeptidic inhibitors exhibit antifungal activity.
UR - http://www.scopus.com/inward/record.url?scp=0032510384&partnerID=8YFLogxK
U2 - 10.1021/jm980001q
DO - 10.1021/jm980001q
M3 - Article
C2 - 9526574
AN - SCOPUS:0032510384
SN - 0022-2623
VL - 41
SP - 996
EP - 1000
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 6
ER -