Protection of asparagine and glutamine during Nα‐Bpoc‐based solid‐phase peptide synthesis

In this paper we describe the synthesis and properties of Bpoc-Asn(Trt)-OH, Bpoc-Asn(Trt)-OPfp, Bpoc-Gln(Trt)-OH and Bpoc-Gln(Trt)-OPfp. These derivatives are highly soluble in CH2Cl2 and can be coupled efficiently in solid-phase peptide synthesis. The peptides, acetyl-Ala-Phe-Asn(Trt)-Gly-Leu-Ala-O-Dbf-SH and Boc-Cys(Acm)-Ala-Phe-Gln(Trt)-Gly-Leu-Ala-O-Dbf-SH (where O-Dbf-SH is the peptide ester of 4-mercapto-6-hydroxydibenzofuran) were synthesized by stepwise solid-phase peptide synthesis using N alpha-Bpoc amino acids. We have observed that less than 0.1% of the trityl group is removed from the carboxamide of Gln and Asn during a standard 15 min N alpha-Bpoc deprotection in 0.5% TFA in CH2Cl2.

[1]  N. Fotouhi,et al.  Practical preparation and deblocking conditions for N-α-2-(p-biphenylyl)-2-propyloxycarbonyl)-amino acid(N-α-Bpoc-Xxx-OH) derivatives , 2009 .

[2]  N. Fotouhi,et al.  Resolution of proline acylation problem for thiol capture strategy by use of a chloro-dibenzofuran template. , 2009, International journal of peptide and protein research.

[3]  O. Seitz,et al.  A Novel Allylic Anchor for Solid‐Phase Synthesis—Synthesis of Protected and Unprotected O‐Glycosylated Mucin‐Type Glycopeptides , 1995 .

[4]  N. Fotouhi,et al.  Novel class of silicon-based protective groups for the side chain of tyrosine. , 1993, International journal of peptide and protein research.

[5]  D. Kemp,et al.  Synthesis of a 39-peptide and a 25-peptide by thiol capture ligations : observation of a 40-fold rate acceleration of the intramolecular O,N-acyl-transfer reaction between peptide fragments bearing only cysteine protective groups , 1993 .

[6]  D. Kemp,et al.  Resolution of the histidine problem for thiol capture--synthesis of a 39-peptide , 1991 .

[7]  P. Sieber,et al.  PROTECTION OF CARBOXAMIDE FUNCTIONS BY THE TRITYL RESIDUE. APPLICATION TO PEPTIDE SYNTHESIS , 1991 .

[8]  N. Fotouhi,et al.  Peptide synthesis by prior thiol capture. 6. Rates of the disulfide-bond-forming capture reaction and demonstration of the overall strategy by synthesis of the C-terminal 29-peptide sequence of BPTI , 1989 .

[9]  D. Kerkman,et al.  Rational design of templates for intramolecular O,N-acyl transfer via medium-sized cyclic intermediates derived from L-cysteine. Definition of an experimental maximum in effective molarity through the study of "tunable" templates , 1989 .

[10]  R. Colombo.  Synthesis by an improved solid-phase method of a highly acidic peptide from nucleolar nonhistone protein C23 , 1981 .

[11]  B. Riniker,et al.  Synthese von Humaninsulin. III. Aufbau des geschützten zweikettigen Fragments A(14‐21) ‐ B(17‐30) , 1976 .

[12]  S. S. Wang,et al.  PREPARATION OF PROTECTED PEPTIDE INTERMEDIATES FOR A SYNTHESIS OF THE OVINE PITUITARY GROWTH HORMONE SEQUENCE 96-135 , 1975 .

[13]  S. S. Wang,et al.  Preparation of protected intermediates for a synthesis of the ovine pituitary growth hormone sequence 96-135. , 1975, The Journal of organic chemistry.

[14]  W. König,et al.  Eine neue Amid‐Schutzgruppe , 1970 .

[15]  B. Riniker,et al.  Menschliches Calcitonin. IV Die Synthese von Calcitonin M. Vorläufige Mitteilung , 1968 .

[16]  W. Steglich,et al.  Leicht abspaltbare Schutzgruppen für die Säureamidfunktion, 2. Vergleichende Untersuchungen zur Abspaltung substit. Benzylreste vom Amidstickstoff und deren Kombinationsmöglichkeiten mit Urethanschutzgruppen , 1968 .

[17]  B. Iselin,et al.  Selektive acidolytische spaltung von aralkyloxycarbonyl‐aminoschutzgruppen , 1968 .

[18]  Y. Shimonishi,et al.  Studies on the Synthesis of Peptides Containing Glutamine as the C-Terminal. I. Protection of Amide-nitrogen with Xanthyl Group during Peptide Synthesis , 1962 .

[19]  R. Sheppard,et al.  Peptides—XXXVI: Synthesis of the 27–37 fragment of a lysozyme analogue , 1979 .