Multigram-scale synthesis of short peptides via a simplified repetitive solution-phase procedure.
A rapid repetitive solution-phase synthesis of peptides is described. The procedure involves coupling of amino acids and peptide acids, instead of the usual amino esters and peptide esters, to slight excesses of pentafluorophenyl active esters in a THF/water solvent mixture. Due to their poor solubility, peptide acid intermediates are easily isolated in high purity by acidification under controlled conditions and removal of excess active esters by selective extraction. Contrary to modern repetitive solution-phase peptide synthesis procedures, our approach does not require time-consuming neutralization reactions and reduces significantly the number of operation units that are necessary to obtain peptide intermediates. Efficiency of the method was demonstrated by the rapid synthesis of short hydrophobic and hydrophilic peptides, the antimalarial cycloheptapeptide mahafacyclin B, and a protected form of the hydrophilic pentapeptide GRGDS.
Meneses
Célia
C
School of Natural and Computing Sciences, University of Aberdeen, Meston Building, Aberdeen, AB24 3UE.
Nicoll
Sarah L
SL
Trembleau
Laurent
L
D000595:Amino Acid Sequence; D004952:Esters; D057927:Hydrophobic and Hydrophilic Interactions; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry*; D012995:Solubility; D012996:Solutions / Q000737:chemistry*; D012997:Solvents; D013237:Stereoisomerism
D004952:Esters; D009842:Oligopeptides; D010455:Peptides; D010456:Peptides, Cyclic; D012996:Solutions; D012997:Solvents; C512387:mahafacyclin B