Comparative study of methods to couple hindered peptides

Spencer, Jeffrey R.; Antonenko, Valery V.; Delaet, Nancy G. J.; Goodman, Murray

doi:10.1111/j.1399-3011.1992.tb00303.x

Cited by 71 publications

(7 citation statements)

References 15 publications

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“…232 This amino acid can be readily incorporated using standard peptide synthesis protocols. 233 It has been demonstrated, that the presence of even a single Aib residue into heptapeptide/ octapeptide sequences induces helical structure. 229 Indeed, the presence of an additional methyl group of the C α carbon makes Aib a natural and noncoded amino acid with the highest helical propensity.…”

Section: Molecular Pharmaceuticsmentioning

confidence: 99%

Glucagon-Like Peptide-1 Receptor Agonists and Strategies To Improve Their Efficiency

2019

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Type 2 diabetes mellitus (T2DM) is increasing in global prevalence and is associated with serious health problems (e.g., cardiovascular disease). Various treatment options are available for T2DM, including the incretin hormone glucagon-like peptide-1 (GLP-1). GLP-1 is a therapeutic peptide secreted from the intestines following food intake, which stimulates the secretion of insulin from the pancreas. The native GLP-1 has a very short plasma half-life, owning to renal clearance and degradation by the enzyme dipeptidyl peptidase-4. To overcome this issue, various GLP-1 agonists with increased resistance to proteolytic degradation and reduced renal clearance have been developed, with several currently marketed. Strategies, such as controlled release delivery systems, methods to reduce renal clearance (e.g., PEGylation and conjugation to antibodies), and methods to improve proteolytic stability (e.g., stapling, cyclization, and glycosylation) provide means to further improve the ability of GLP-1 analogs. These will be discussed in this literature review.

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Section: Molecular Pharmaceuticsmentioning

confidence: 99%

Glucagon-Like Peptide-1 Receptor Agonists and Strategies To Improve Their Efficiency

2019

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“…The previous methods involved high temperatures (50 C) or long reaction times (seven days) in combination with a large excess of UNCAs. 131 Similarly, the Zn dust method could be applied for coupling involving N-methyl amino acid esters to obtain good yields of dipeptides. 34 (N a -Alloc)-NMe-amino acid esters were coupled with Fmoc-amino acid uorides using Pd(PPh 3 ) 4 as catalyst in the presence of PhSiH 3 and this gave good yields.…”

Section: Coupling Involving Extremely Hindered Amino Acidsmentioning

confidence: 99%

Amino acid fluorides: viable tools for synthesis of peptides, peptidomimetics and enantiopure heterocycles

et al. 2015

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“…That is consistent with the report of Spencer et al . (24) who studied the methods for coupling hindered peptides. The coupling of the third amino acid residue to H‐Tyr( t Bu)‐dmP‐OMe would be very problematic because this dipeptide ester is unusually prone to give diketopiperazine.…”

Section: Combined Solution Synthesis and Spps Of 3amentioning

confidence: 99%

A convenient incorporation of conformationally constrained 5,5‐dimethylproline into the ribonuclease A 89–124 sequence by condensation of synthetic peptide fragments

Čeřovský

Welker

Scheraga

2003

The Journal of Peptide Research

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The presence of l-5,5-dimethylproline (dmP) within an amino acid sequence results in the formation of an X-dmP peptide bond predominantly locked in a cis conformation. However, the common use of this unnatural amino acid has been hampered by the difficulty of the economical incorporation of the dmP residue into longer peptide segments due to the steric hindrance imposed by the dimethyl moieties. Here, we describe synthesis of the C-terminal 36-residue peptide, corresponding to the 89-124 sequence of bovine pancreatic ribonuclease A (RNase A), in which dmP is incorporated as a substitute for Pro93. The peptide was assembled by condensation of protected 5- and 31-residue peptide fragments, which were synthesized by solid-phase peptide methodology using fluorenylmethyloxycarbonyl chemistry. We focused on optimizing the synthesis of the Fmoc-Ser(tBu)-Ser(tBu)-Lys(Boc)-Tyr(tBu)-dmP-OH pentapeptide (residues 89-93) with efficient acylation of the sterically hindered dmP residue. In a comparative study, the reagent O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate was found to be superior to bromo-tris-pyrrolidino-phosphonium hexafluorophosphate and tetramethylfluoroformamidinium hexafluorophosphate for the synthesis of the -Tyr(tBu)-dmP- peptide bond in solution as well as on a resin.

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Comparative study of methods to couple hindered peptides

Cited by 71 publications

References 15 publications

Glucagon-Like Peptide-1 Receptor Agonists and Strategies To Improve Their Efficiency

Glucagon-Like Peptide-1 Receptor Agonists and Strategies To Improve Their Efficiency

Amino acid fluorides: viable tools for synthesis of peptides, peptidomimetics and enantiopure heterocycles

A convenient incorporation of conformationally constrained 5,5‐dimethylproline into the ribonuclease A 89–124 sequence by condensation of synthetic peptide fragments

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