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A novel synthesis of thymosin alpha 1 by classical methods using seven tert.-butyl side chain protected fragments is described. Optimum conditions were found for the final DCC/HOBt coupling of the two key intermediates; decapeptide and octadecapeptide. Thymosin alpha 1 was purified by two stages of preparative HPLC (partial purification with C8 and final purification with C18 reverse phase silica gel) to give a 30% overall yield for the final four stages of synthesis (including catalytic hydrogenation of octadecapeptide, coupling, deprotection and purification). The product was shown to be homogeneous by thin-layer and paper high voltage electrophoresis, isoelectric focusing analysis, thin-layer chromatography and high performance liquid chromatography. Amino acid analysis, optical rotation, 1H-n.m.r. spectroscopy, FAB mass spectroscopy and peptide mapping after tryptic digestion confirmed the structure of thymosin alpha 1. Three minor stereoisomer contaminants were isolated by HPLC and characterized as [D-Lys14]-thymosin alpha 1, [D-Lys17]-thymosin alpha 1 and [D-Ala3]-thymosin alpha 1 resulting from racemization at Lys14, Lys17 and Ala3 during the coupling of the fragments. A final contaminant, isolated by HPLC, was characterized as N alpha-isobutyloxycarbonyl-thymosin alpha 1 (15-28), which results from "wrong way opening" of an activated mixed anhydride.
A M Felix, and
E P Heimer, and
C T Wang, and
T J Lambros, and
J Swistok, and
M Roszkowski, and
M Ahmad, and
D Confalone, and
J W Scott, and
D Parker
July 1980,
Biochemistry,
A M Felix, and
E P Heimer, and
C T Wang, and
T J Lambros, and
J Swistok, and
M Roszkowski, and
M Ahmad, and
D Confalone, and
J W Scott, and
D Parker
January 1980,
International journal of peptide and protein research,
A M Felix, and
E P Heimer, and
C T Wang, and
T J Lambros, and
J Swistok, and
M Roszkowski, and
M Ahmad, and
D Confalone, and
J W Scott, and
D Parker
August 2015,
Organic & biomolecular chemistry,
A M Felix, and
E P Heimer, and
C T Wang, and
T J Lambros, and
J Swistok, and
M Roszkowski, and
M Ahmad, and
D Confalone, and
J W Scott, and
D Parker
May 2018,
European journal of medicinal chemistry,
A M Felix, and
E P Heimer, and
C T Wang, and
T J Lambros, and
J Swistok, and
M Roszkowski, and
M Ahmad, and
D Confalone, and
J W Scott, and
D Parker
February 2003,
The Journal of organic chemistry,
A M Felix, and
E P Heimer, and
C T Wang, and
T J Lambros, and
J Swistok, and
M Roszkowski, and
M Ahmad, and
D Confalone, and
J W Scott, and
D Parker
January 2011,
Acta crystallographica. Section E, Structure reports online,
A M Felix, and
E P Heimer, and
C T Wang, and
T J Lambros, and
J Swistok, and
M Roszkowski, and
M Ahmad, and
D Confalone, and
J W Scott, and
D Parker
January 2001,
Chirality,
A M Felix, and
E P Heimer, and
C T Wang, and
T J Lambros, and
J Swistok, and
M Roszkowski, and
M Ahmad, and
D Confalone, and
J W Scott, and
D Parker
February 2020,
Molecules (Basel, Switzerland),
A M Felix, and
E P Heimer, and
C T Wang, and
T J Lambros, and
J Swistok, and
M Roszkowski, and
M Ahmad, and
D Confalone, and
J W Scott, and
D Parker
January 1980,
International journal of peptide and protein research,
A M Felix, and
E P Heimer, and
C T Wang, and
T J Lambros, and
J Swistok, and
M Roszkowski, and
M Ahmad, and
D Confalone, and
J W Scott, and
D Parker
May 1978,
International journal of peptide and protein research,
