A practical total synthesis of the microbial alkaline proteinase inhibitor (MAPI).
Diverse serine and cysteine proteases as well as alkaline proteinases and elastases play a crucial role in numerous biological processes. Natural peptide aldehydes such as the "microbial alkaline proteinase inhibitor" (MAPI, 1) are valuable tools to characterize novel enzymes and to study their function in nature. Within a drug discovery program we wanted to design and explore non-natural MAPI congeners with novel biological profiles. To that end we devised a simple, practical, and scalable synthesis of MAPI 1 from readily available amino acid building blocks. The modular nature of our approach allows convenient structural modification of the MAPI backbone.
Haebich
Dieter
D
Bayer Schering Pharma AG, Medicinal Chemistry, 42096 Wuppertal, Germany. dieter.haebich@bayerhealthcare.com
Hillisch
Alexander
A
El Sheikh
Sherif
S
D000596:Amino Acids / Q000737:chemistry; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000494:pharmacology; D011485:Protein Binding
D000596:Amino Acids; D001426:Bacterial Proteins; D010455:Peptides; C038356:microbial alkaline proteinase inhibitor; D010450:Endopeptidases; C087822:alkaline protease