Peptide-drug conjugation: a strategy to address blood-brain barrier limitations in central nervous system diseases

Central nervous system diseases are among the most challenging to treat, mainly due to the blood-brain barrier, which restricts the entry of most therapeutics into the brain, preventing them from reaching pharmacological concentrations. Moreover, the multifactorial causes of these diseases require targeting diverse key processes. In this context, peptide-drug conjugates represent a promising strategy and offer a multitargeting regimen platform. In this work, we describe the latest developments of peptide-drug conjugates for glioma, Alzheimer's, and Parkinson's diseases, highlighting how conjugating payloads to specific peptides can offer several therapeutic advantages over conventional approaches. Particular emphasis was given to the chemical nature of the conjugation bonds and to the synthetic reactions to underscore the versatility of the methods used.