2021
DOI: 10.3390/molecules26061591
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Recent Advances and Trends in Chemical CPP–Drug Conjugation Techniques

Abstract: This review summarizes recent developments in conjugation techniques for the synthesis of cell-penetrating peptide (CPP)–drug conjugates targeting cancer cells. We will focus on small organic molecules as well as metal complexes that were used as cytostatic payloads. Moreover, two principle ways of coupling chemistry will be discussed direct conjugation as well as the use of bifunctional linkers. While direct conjugation of the drug to the CPP is still popular, the use of bifunctional linkers seems to gain inc… Show more

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Cited by 15 publications
(13 citation statements)
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References 119 publications
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“…After that, other CPPs with different properties in charge, polarity, and structure were reported to deliver bioactive molecules as classified in the CPPsite 2.0 database ( https://webs.iiitd.edu.in/raghava/cppsite/index.html ). CPPs are capable of delivering therapeutic substances (drugs or vaccines) into cellular compartments using the covalent or non-covalent linkage [ 8 11 ].…”
Section: Introductionmentioning
confidence: 99%
See 1 more Smart Citation
“…After that, other CPPs with different properties in charge, polarity, and structure were reported to deliver bioactive molecules as classified in the CPPsite 2.0 database ( https://webs.iiitd.edu.in/raghava/cppsite/index.html ). CPPs are capable of delivering therapeutic substances (drugs or vaccines) into cellular compartments using the covalent or non-covalent linkage [ 8 11 ].…”
Section: Introductionmentioning
confidence: 99%
“…html). CPPs are capable of delivering therapeutic substances (drugs or vaccines) into cellular compartments using the covalent or non-covalent linkage [8][9][10][11].…”
Section: Introductionmentioning
confidence: 99%
“…Despite such promises, low selectivity of half‐sandwich metal complexes for cancer cells is a challenge to overcome. In recent years, attempts to increase accumulation in cancer cells by conjugation of metal complexes with biological molecules such as proteins, [40–42] peptides, [43–46] or sugars [47] have been investigated. Glycoconjugation or functionalisation of drugs with carbohydrates has been shown to be a particularly promising approach for increasing the cellular uptake of a drug by cancer cells [48–54] .…”
Section: Introductionmentioning
confidence: 99%
“…CPPs have been identified as safe and effective delivery vehicles, and utilized in both in vitro and in vivo delivery of various cargos including peptides [13] , proteins [14] , small organic molecules [15] , antisense oligonucleotides [16] , fluorescent dyes [17] or small interfering RNAs [18] . For delivery of protein or peptides, CPPs can be directly conjugated to the C-terminus of protein or peptide.…”
Section: Introductionmentioning
confidence: 99%
“…In addition, CPP-drug conjugates can be formulated with a variety of conjugation techniques including amid bond, bifunctional succinyl linker, disulfide linker or maleimide linker, etc. [15] . Direct conjugation of CPPs with therapeutic agents have significantly improved the solubility, stability and permeability.…”
Section: Introductionmentioning
confidence: 99%