Reactifs de couplage peptidique I (1) - l'hexafluorophosphate de benzotriazolyl N-oxytrisdimethylamino phosphonium (B.O.P.)

Castro, Bertrand; Dormoy, Jean‐Robert; Evin, Geneviève; Selve, C.

doi:10.1016/s0040-4039(00)72100-9

Cited by 686 publications

(285 citation statements)

References 10 publications

Supporting

Mentioning

268

Contrasting

Unclassified

Order By: Relevance

“…One cycle of the synthesis using 15-20 mL solvent per gram of resin consisted of the following two operations: (a) a 20-min deprotection with 50% trifluoroacetic acid/CH2CI2, and (b) coupling with 4 equiv. each of Boc-amino acid and BOP (Castro et al, 1975) in the presence of 12 equiv. DIEA in DMF for 45-60 min.…”

Section: Peptide Synthesis and General Proceduresmentioning

confidence: 99%

A biomimetic strategy in the synthesis and fragmentation of cyclic protein

1998

View full text Add to dashboard Cite

This paper describes a simple biomimetic strategy to prepare small cyclic proteins containing multiple disulfide bonds. Our strategy involves intramolecular acyl transfer reactions to assist both the synthesis and fragmentation of these highly constrained cyclic structures in aqueous solution. To illustrate our strategy, we synthesized the naturally occurring circulin B and cyclopsychotride (CPT), both consisting of 3 1 amino acid residues tightly packed in a cystine-knot motif with three disulfide bonds and an end-to-end cyclic form. The synthesis of these small cyclic proteins can be achieved by orthogonal ligation of free peptide thioester via the thia zip reaction, which involves a series of reversible thiolthiolactone exchanges to arrive at an a-amino thiolactone, which then undergoes an irreversible, spontaneous ring contraction through an S,N-acyl migration to form the cyclic protein. A two-step disulfide formation strategy is employed for obtaining the desired disulfide-paired products. Partial acid hydrolysis through intramolecular acyl transfer of X-Ser, X-Thr, Asp-X, and Glu-X sequences is used to obtain the assignment of the circulins disulfide bond connectives. Both synthetic circulin B and CPT are identical to the natural products and, thus, the total synthesis confirms the disulfide connectivity of circulin B and CPT contain a cystine-knot motif of 1-4,2-5, and 3-6. In general, our strategy, based on the convergence of chemical proteolysis and aminolysis of peptide bonds through acyl transfer, is biomimetic and provides a useful approach for the synthesis and characterization of large end-to-end cyclic peptides and small proteins.

show abstract

Section: Peptide Synthesis and General Proceduresmentioning

confidence: 99%

A biomimetic strategy in the synthesis and fragmentation of cyclic protein

1998

View full text Add to dashboard Cite

show abstract

“…Assembly of the protected peptide chain corresponding to residues 18-99 was achieved on an AB1 430A peptide synthesizer, using optimized tert-butoxycarbonyl (Boc) chemistry protocols (Kent, 1988). Boc-protected BTD was coupled manually using BOP activation (Castro et al, 1975), following which the chain assembly was completed by manually coupling residues 1 -15 as hydroxybenzotriazole esters. The Gly16,17-containing monomer sequence was synthesized from another portion of the same (residues 18-99) peptide resin on the peptide synthesizer.…”

Section: Protein Synthesismentioning

confidence: 99%

Structural engineering of the HIV‐1 protease molecule with a β‐turn mimic of fixed geometry

1993

View full text Add to dashboard Cite

An important goal in the de novo design of enzymes is the control of molecular geometry. To this end, an analog of the protease from human immunodeficiency virus 1 (HIV-1 protease) was prepared by total chemical synthesis, containing a constrained, nonpeptidic type 11' 0-turn mimic of predetermined three-dimensional structure.The mimic &turn replaced residues GlyI6,l7 in each subunit of the homodimeric molecule. These residues constitute the central amino acids of two symmetry-related type I' 0-turns in the native, unliganded enzyme. The 0-turn mimic-containing enzyme analog was fully active, possessed the same substrate specificity as the GlyI67l7-containing enzyme, and showed enhanced resistance to thermal inactivation. These results indicate that the precise geometry of the @turn at residues 15-18 in each subunit is not critical for activity, and that replacement of the native sequence with a rigid 0-turn mimic can lead to enhanced protein stability. Finally, the successful incorporation of a fixed element of secondary structure illustrates the potential of a "molecular kit set" approach to protein design and synthesis.

show abstract

“…The coupling reagents 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) [39] and benzotriazol-1-yl-oxy-tris-(diA C H T U N G T R E N N U N G methA C H T U N G T R E N N U N G ylA C H T U N G T R E N N U N G amiA C H T U N G T R E N N U N G no)phosphonium hexafluorophosphate (BOP), [40] N-hydroxybenzotriazole (HOBt), and N a -9-fluorenylmethyloxycarbonyl (Fmoc) amino acids were obtained from GL Biochem Ltd. (Shanghai, China). The Fmocprotected l-and d-allylglycine (Alg) were purchased from Neosystem Laboratoire (Strasbourg, France).…”

mentioning

confidence: 99%

Synthesis of Bicyclic Alkene‐/Alkane‐Bridged Nisin Mimics by Ring‐Closing Metathesis and their Biochemical Evaluation as Lipid II Binders: toward the Design of Potential Novel Antibiotics

et al. 2007

View full text Add to dashboard Cite

This report describes the design, synthesis, and biochemical evaluation of alkene‐ and alkane‐bridged AB(C)‐ring mimics of the lantibiotic nisin. Nisin belongs to a class of natural antimicrobial peptides, and has a unique mode of action: its AB(C)‐ring system binds to the pyrophosphate moiety of lipid II. This mode of action was the rationale for the design of smaller nisin‐derived peptides to obtain novel potential antibiotics. As a conformational constraint the thioether bridge was mimicked by an alkene‐ or alkane isostere. The peptides of the linear individual ring precursors were synthesized on solid support or in solution, and cyclized by ring‐closing metathesis in solution with overall yields of between 36 and 89 %. The individual alkene‐bridged macrocycles were assembled in solution by using carbodiimide‐based synthesis protocols for the corresponding AB(C)‐ring mimics. These compounds were tested for their binding affinity toward lipid II by evaluation of their potency to inhibit nisin‐induced carboxyfluorescein release from large unilamellar vesicles. It was found that these AB(C)‐ring mimics were not able to induce membrane leakage; however, they acted by inhibiting nisin‐induced carboxyfluorescein release; this indicates their affinity toward lipid II. These results imply that an alkene or alkane moiety is a suitable thioether bridge mimic.

show abstract

Reactifs de couplage peptidique I (1) - l'hexafluorophosphate de benzotriazolyl N-oxytrisdimethylamino phosphonium (B.O.P.)

Cited by 686 publications

References 10 publications

A biomimetic strategy in the synthesis and fragmentation of cyclic protein

A biomimetic strategy in the synthesis and fragmentation of cyclic protein

Structural engineering of the HIV‐1 protease molecule with a β‐turn mimic of fixed geometry

Synthesis of Bicyclic Alkene‐/Alkane‐Bridged Nisin Mimics by Ring‐Closing Metathesis and their Biochemical Evaluation as Lipid II Binders: toward the Design of Potential Novel Antibiotics

Contact Info

Product

Resources

About