Macrocyclic Peptides as Drug Candidates: Recent Progress and Remaining Challenges

Peptides as a therapeutic modality attract much attention due to their synthetic accessibility, high degree of specific binding, and the ability to target protein surfaces traditionally considered "undruggable". Unfortunately, at the same time, other pharmacological properties of a generic peptide, such as metabolic stability and cell permeability, are quite poor, which limits the success of de novo discovered biologically active peptides as drug candidates. Here, we review how macrocyclization as well as the incorporation of nonproteogenic amino acids and various conjugation strategies may be utilized to improve on these characteristics to create better drug candidates. We analyze recent progress and…

• JA
  Japan Agency for Medical Research and Development

  Awards: am0301001h0004, am0101090j0001
• JS
  Japan Society for the Promotion of Science

  Award: 26220204
• CR
  Core Research for Evolutional Science and Technology

  Award: JPMJCR12L2