Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• its native binding partner β-catenin. An increased proteolytic stability against proteinase K has been demonstrated. Keywords: accelerated molecular dynamics; halotryptophan; intrinsically disordered peptides; late-stage diversification; macrocyclisation; molecular dynamics; stapled peptides; Suzuki

• . The conformational preferences of the stapled peptide P5 and of the linear peptides P6 and aAxWt were investigated via extensive accelerated molecular dynamics simulations (aMD) as implemented within the Amber18 program package [85]. The aMD methodology developed by McCammon and co-workers [86] has

• of the three cleavage sites are blocked by the macrocycle. Accelerated molecular dynamics simulations verified a significantly higher degree of helicity for SMC stapled peptide P5 compared to the linear analogues P6 and aAxWt, which is in accordance with the experimental data obtained from CD and

Computational methods in drug discovery

• Sumudu P. Leelananda and
• Steffen Lindert

Beilstein J. Org. Chem. 2016, 12, 2694–2718, doi:10.3762/bjoc.12.267

• methods of enhanced sampling are introduced in literature, including: accelerated molecular dynamics [196][197], metadynamics [198][199], umbrella sampling [200] and temperature-accelerated molecular dynamics [201][202]. Accelerated molecular dynamics (aMD) simulations reduce the energy barrier of wells