Synthesis and Biological Activity of N-Sulfonyltripeptides with C-Terminal Arginine as Potential Serine Proteases Inhibitors

Markowska, Agnieszka; Bruzgo, Magdalena; Gorodkiewicz, Ewa; Surażyński, Arkadiusz

doi:10.1007/s10989-012-9338-4

Cited by 5 publications

(2 citation statements)

References 33 publications

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“…Phage-display peptide screening has been successfully used for the discovery of KLK2-inhibiting peptides as promising imaging probes for use in prostate cancer 192,193 . De novo solidphase synthesis efforts for the development of peptidebased KLK inhibitors are exemplified by: the synthesis of LEKTI-peptide domain 6 as a potent KLK5 and KLK7 inhibitor; the design of azapeptide-based inhibitors of KLK3; and the development of KLK1 inhibitors (for example, compound 1 in TABLE 2) from modified N-sulfonyltripeptides [194][195][196] .…”

Section: Peptide-based Klk Inhibitorsmentioning

confidence: 99%

Unleashing the therapeutic potential of human kallikrein-related serine proteases

Prassas

Eissa

Poda

et al. 2015

Nat Rev Drug Discov

201

183

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Tissue kallikreins are a family of fifteen secreted serine proteases encoded by the largest protease gene cluster in the human genome. In the past decade, substantial progress has been made in characterizing the natural substrates, endogenous inhibitors and in vivo functions of kallikreins, and studies have delineated important pathophysiological roles for these proteases in a variety of tissues. Thus, kallikreins are now considered attractive targets for the development of novel therapeutics for airway, cardiovascular, tooth, brain, skin and neoplastic diseases. In this Review, we discuss recent advances in our understanding of the physiological functions and pathological implications of kallikrein proteases, and highlight progress in the identification of kallikrein inhibitors, which together are bringing us closer to therapeutically targeting kallikreins in selected disease settings.

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Section: Peptide-based Klk Inhibitorsmentioning

confidence: 99%

Unleashing the therapeutic potential of human kallikrein-related serine proteases

Prassas

Eissa

Poda

et al. 2015

Nat Rev Drug Discov

201

183

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“…The syringe was placed on a rotator and slowly agitated (ten turns/min) for 2 h. The resin was washed three times with DMF and once with DCM. Completion of the reaction was monitored by trinitrobenzene sulfonic acid (TNBS) test [21] except for the coupling of Fmoc-Asp(OAll)-OH on H-Pro-Rink amide resin, which was monitored by the chloranil assay [22] to check acylation of the secondary amine.…”

Section: Coupling Stepmentioning

confidence: 99%

A switchable stapled peptide

et al. 2016

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The O-N acyl transfer reaction has gained significant popularity in peptide and medicinal chemistry. This reaction has been successfully applied to the synthesis of difficult sequence-containing peptides, cyclic peptides, epimerization-free fragment coupling and more recently, to switchable peptide polymers. Herein, we describe a related strategy to facilitate the synthesis and purification of a hydrophobic stapled peptide. The staple consists of a serine linked through an amide bond formed from its carboxylic acid function and the side chain amino group of diaminopropionic acid and through an ester bond formed from its amino group and the side chain carboxylic acid function of aspartic acid. The α-amino group of serine was protonated during purification. Interestingly, when the peptide was placed at physiological pH, the free amino group initiated the O-N shift reducing the staple length by one atom, leading to a more hydrophobic stapled peptide.

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