TY - JOUR
T1 - Evaluation of two new coupling agents for incorporation of α,α-dialkylamino acids, such as α-methylalanine, in solid-phase peptide synthesis
AU - Sapia, Alan C.
AU - Slomczynska, Urszula
AU - Marshall, Garland R.
PY - 1995/5
Y1 - 1995/5
N2 - The introduction of solid-phase peptide synthesis (SPPS) has greatly facilitated the preparation of peptides containing proteinaceous amino acids. Less common, sterically hindered α,α-dialkylamino acids, such as α-methylalanine (MeA, aminoisobutyric acid, Aib), have proven a synthetic challenge for incorporation by this approach, especially when present in contiguous sequences. Solution protocols, utilizing highly reactive intermediates such as oxazalones, are generally used during the preparation of peptaibol antibiotics such as alamethicin, emerimicin, etc. which contain such contiguous sequences. Two recently developed coupling strategies (O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate, HATU, and Fmoc-protected amino acid fluorides) allow peptides comprising contiguous sequences of α,α-dialkylamino acids to be prepared using SPPS. The present study evaluates the relative merits of these two methods on a set of difficult peptides containing oligo-MeA sequences.
AB - The introduction of solid-phase peptide synthesis (SPPS) has greatly facilitated the preparation of peptides containing proteinaceous amino acids. Less common, sterically hindered α,α-dialkylamino acids, such as α-methylalanine (MeA, aminoisobutyric acid, Aib), have proven a synthetic challenge for incorporation by this approach, especially when present in contiguous sequences. Solution protocols, utilizing highly reactive intermediates such as oxazalones, are generally used during the preparation of peptaibol antibiotics such as alamethicin, emerimicin, etc. which contain such contiguous sequences. Two recently developed coupling strategies (O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate, HATU, and Fmoc-protected amino acid fluorides) allow peptides comprising contiguous sequences of α,α-dialkylamino acids to be prepared using SPPS. The present study evaluates the relative merits of these two methods on a set of difficult peptides containing oligo-MeA sequences.
KW - Amino acid fluoride
KW - Aminoisobutyric acid
KW - Coupling reagents
KW - Emerimicin
KW - HATU
KW - Peptaibol
KW - α,α-Dialkylamino acids
KW - α-Methylalanine
UR - http://www.scopus.com/inward/record.url?scp=0000290067&partnerID=8YFLogxK
U2 - 10.1007/BF00119769
DO - 10.1007/BF00119769
M3 - Article
AN - SCOPUS:0000290067
SN - 0929-5666
VL - 1
SP - 283
EP - 290
JO - Letters in Peptide Science
JF - Letters in Peptide Science
IS - 6
ER -