Merrifield referred to the work of Steve Kent and of James Tam. Two key
references are below but there may be more recent modifications and
applications of the techniques. Merrifield failed to acknowledge an
alternative strategy developed in (formerly) Bob Sheppard's lab. In this
approach peptide segments are made with with acetyl-Hmb backbone
protection at suitable positions. This confers high solubility on the
segments in organic solvent and so enhances dramatically the yield of any
ligation step. Once ligated, the Hmb groups are removed. Assembly is
generally at C-terminal Gly or Pro, but techniques exist for ligation at
other residues with low racemisation. Be aware that the Tam and Kent
techniques do not always involve the formation of natural peptide bonds or
residues
Len.
TI: SYNTHESIS OF PROTEINS BY NATIVE CHEMICAL LIGATION
AU: DAWSON_PE, MUIR_TW, CLARKLEWIS_I, KENT_SBH
JN: SCIENCE, 1994, Vol.266, No.5186, pp.776-779
TI: PEPTIDE-SYNTHESIS USING UNPROTECTED PEPTIDES THROUGH ORTHOGONAL
COUPLING METHODS
AU: TAM_JP, LU_YA, LIU_CF, SHAO_J
JN: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES
OF AMERICA, 1995, Vol.92, No.26, pp.12485-12489
TI: SOLID-PHASE ASSEMBLY OF BACKBONE AMIDE-PROTECTED PEPTIDE SEGMENTS -
AN EFFICIENT AND RELIABLE STRATEGY FOR THE SYNTHESIS OF SMALL
PROTEINS
AU: QUIBELL_M, PACKMAN_LC, JOHNSON_T
JN: JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1996, No.11,
pp.1227-1234
TI: SYNTHESIS OF THE 3-REPEAT REGION OF HUMAN TAU-2 BY THE SOLID-PHASE
ASSEMBLY OF BACKBONE AMIDE-PROTECTED SEGMENTS
AU: QUIBELL_M, PACKMAN_LC, JOHNSON_T
JN: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1995, Vol.117, No.47,
pp.11656-11668
TI: IDENTIFICATION OF COUPLING CONDITIONS PROCEEDING WITH LOW C-TERMINAL
EPIMERIZATION DURING THE ASSEMBLY OF FULLY PROTECTED BACKBONE-
SUBSTITUTED PEPTIDE SEGMENTS
AU: QUIBELL_M, PACKMAN_LC, JOHNSON_T
JN: JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1996, No.11,
pp.1219-1225
*********************************************************************
Dr Len C. Packman
Assistant Director of Research
Protein and Nucleic Acid Chemistry Facility
Department of Biochemistry
University of Cambridge
80 Tennis Court Road
Old Addenbrookes Site
Cambridge, CB2 1GA, UK
Tel: +44 (1223) 333639 (including answerphone)
FAX: +44 (1223) 766002
e-mail: lcp2@mole.bio.cam.ac.uk
Visit my WWW page at http://www.bio.cam.ac.uk/proj/adr/PNAC/pnac.html