Chemical Approaches to Macrocycle Libraries

Qian, Ziqing; Dougherty, Patrick G; Pei, Dehua

doi:10.1002/9781119092599.ch6

Cited by 1 publication

(2 citation statements)

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“…Herein, the term cyclic is restricted to a description of macrocyclic CPPs and bioportides that possess no obvious N-or C-termini ( Figure 1B). As expertly reviewed, [55] potent but cell-permeable inhibitor of oncogenic K-Ras. [56] Finally, it is noteworthy that a comparison [57] of the uptake mechanisms of chemically diverse cyclic CPPs, synthesised using native chemical ligation of N-and C-termini, revealed that cyclisation generally improved uptake efficiency but illuminated different structural requirements to promote either glycosaminoglycan (GAG)-dependent endocytosis or direct membrane translocation.…”

Section: Helical Stapled and Cyclic Peptidesmentioning

confidence: 99%

“…However, progress towards clinical utility will likely require chemical modifications to improve both pharmacokinetic and pharmacodynamic parameters. [25,26,55] As evidenced by many of the studies summarised herein, no consensus is available to direct such modifications which are consistently challenging in a conventional academic environment. Drug discovery, of which bioportide technologies is surely a viable component, [58,93,94] could and should be markedly accelerated if governments, pharmaceutical companies and funding agencies were challenged to work with academics to more freely provide financial support and expertise in drug optimisation and formulation.…”

Section: New Biology In New Directionsmentioning

confidence: 99%

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A new biology of cell penetrating peptides

Howl

Jones

2020

Peptide Science

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As pharmacokinetic modifiers, cell penetrating peptides (CPPs) have proven utility for the delivery of otherwise impermeable cargoes into the discrete intracellular compartments of eukaryotic cells. Methods for the molecular optimisation of CPP sequences can significantly increase the performance of novel vectors matched to a specific delivery function. Moreover, the ‘information rich’ composition and inherent molecular flexibility of many CPPs can also facilitate their interaction with intracellular proteins and other cellular structures. This proteomimetic property of CPPs has been exploited in the design of bioportides, bioactive CPPs that regulate cellular functions often by binding relatively flat PPI interfaces to achieve a dominant negative action. This new biology of CPPs is rapidly gathering momentum through the design and synthesis of a bewildering variety of peptides that may be, in whole or part, linear, helical, cyclic and/or chimeric in nature. A particular emphasis of contemporary CPP‐centred drug discovery is the unmet medical need of cancer, though the biomedical scope of bioportide applications is impressively broad including cellular signalling and reprogramming. We are hopeful that one or more of the fascinating studies described herein will translate into the clinic to establish bioportide technologies as a viable option for drug discovery.

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Section: Helical Stapled and Cyclic Peptidesmentioning

confidence: 99%