[2] Rapid in situ neutralization protocols for Boc and Fmoc solid-phase chemistries

Alewood, Paul F.; Alewood, Dianne; Miranda, Les P.; Love, S. L.; Meutermans, Wim; Wilson, David T.

doi:10.1016/s0076-6879(97)89041-6

Cited by 99 publications

(86 citation statements)

References 21 publications

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“…In 1990, one manufacturer of automated synthesizers illustrated FastMoc chemistry using HBTU with fast coupling times of 10-30 min [3][4][5]. In 1993, the coupling agent O-(7-azabenzotriazole-1-yl)-N ,N ,N N -tetramethyluronium hexafluorophosphate (HATU) was introduced [6], and 4 years later, Kent and Alewood et al reported on an accelerated peptide synthesis with coupling times of 1-2 min using Boc chemistry and HATU [7]. While HATU has also been used as a coupling reagent with Fmoc chemistry [8,9], to our knowledge coupling times less than 15 min were not attempted.…”

Section: Introductionmentioning

confidence: 99%

Fast conventional Fmoc solid‐phase peptide synthesis with HCTU

Hood

Fuentes

Patel

et al. 2007

Journal of Peptide Science

142

119

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1H-Benzotriazolium 1-[bis(dimethyl-amino)methylene]-5-chloro-hexafluorophosphate (1-),3-oxide (HCTU) is a nontoxic, nonirritating and noncorrosive coupling reagent. Seven biologically active peptides (GHRP-6, 65 -74 ACP, oxytocin, G-LHRH, Cpeptide, hAmylin 1 -37 , and β-amyloid 1 -42 ) were synthesized with reaction times reduced to deprotection times of 3 min or less and coupling times of 5 min or less using HCTU as the coupling reagent. Expensive coupling reagents or special techniques were not used. Total peptide synthesis times were dramatically reduced by as much as 42.5 h (1.8 days) without reducing the crude peptide purities. It was shown that HCTU can be used as an affordable, efficient coupling reagent for fast Fmoc solid-phase peptide synthesis.

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Section: Introductionmentioning

confidence: 99%

Fast conventional Fmoc solid‐phase peptide synthesis with HCTU

Hood

Fuentes

Patel

et al. 2007

Journal of Peptide Science

142

119

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“…(Alewood et al, 1997) Briefly, Nα-Fmoc-protected amino acids (4.2eq.) were activated with HBTU/DIPEA (4eq./5eq.)…”

Section: Peptide Synthesismentioning

confidence: 99%

New gonadotropin-releasing hormone glycolipids with direct antiproliferative activity and gonadotropin-releasing potency

Varamini

Mansfeld

Giddam

et al. 2017

International Journal of Pharmaceutics

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Graphical abstractGonadotropin-releasing hormone (GnRH) is an endogenous peptide with a short biological half-life. Although GnRH analogs (eg. triptorelin) are developed with enhanced stability compared to the native peptide, they still suffer from poor biological stability and pharmacokinetic properties. Furthermore, they are only effective in the treatment of hormone-dependent reproductive cancers. In this study we applied lipidation and glycosylation along with D-amino acid substitution at position 6 (D-Trp 6 ) to improve the stability, permeability, and consequently the potency of the GnRH peptide and triptorelin. We showed that the conjugation of GnRH with a lipid moiety and carbohydrates made all modified constructs (1-8) more stable than the parent peptide against enzymatic degradation (5.5 to 6.5 times). Two of the lactose-modified glycolipopeptides, 3 and 6, showed 27 and 16 times higher membrane permeability than the parent GnRH, respectively. All analogs with D-Trp 6 -substitution (4-6) exerted GnRH receptor-mediated antiproliferative activity in prostate and ovarian GnRH-receptor positive cell lines. They were more potent than triptorelin in the hormone-independent prostate cancer cell line: DU145. Compound 6 (lactose-modified) was the most potent analog for stimulating the release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) gonadotropins from rat pituitary cells in vitro. The same glycolipopeptide exhibited a higher efficacy and duration of action in stimulating the release of LH than triptorelin in a preclinical mouse model. The superior activity 2 of lipid-and carbohydrate-substituted triptorelin analog 6 made it a promising candidate for the development of new GnRH agonists to treat both hormone-dependent and hormone-refractory prostate cancer..LIST OF ABBREVIATIONS

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“…)/DIPEA(6 eq.) activation and the in situ neutralisation protocol for Fmoc chemistry [32]. The following protected amino acids (4.…”

Section: Synthesismentioning

confidence: 99%

Synthesis and Plasma Stability of Disulfide-Bridged Cyclic Endomorphin-1 Derivatives

Mansfeld¹,

Tóth²

2012

IJOC

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Endomorphin-1 is an endogenous opioid peptide that mediates pain relief through interaction with the µ-opioid receptor in the central nervous system. To enhance the metabolic stability of this tetrapeptide, cyclisation through the formation of a disulfide bridge between the side chains of cysteine residues added to the sequence was explored. A further increase in stability was achieved through N-terminal modification with lipoamino acid and lactose succinamic acid, and the inclusion of D-amino acids. The latter also provided an alternative spatial arrangement of the aromatic side chains. The lipidated cyclic derivatives were insoluble in aqueous buffer, however, the cyclic peptides and glycopeptides showed greatly improved stability towards enzymatic degradation in human plasma.

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[2] Rapid in situ neutralization protocols for Boc and Fmoc solid-phase chemistries

Cited by 99 publications

References 21 publications

Fast conventional Fmoc solid‐phase peptide synthesis with HCTU

Fast conventional Fmoc solid‐phase peptide synthesis with HCTU

New gonadotropin-releasing hormone glycolipids with direct antiproliferative activity and gonadotropin-releasing potency

Synthesis and Plasma Stability of Disulfide-Bridged Cyclic Endomorphin-1 Derivatives

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