肽-寡核苷酸偶联物的化学研究综述--Chemistry of Peptide-Oligonucleotide Conjugates A Review.pdfVIP

molecules

Review

ChemistryofPeptide-OligonucleotideConjugates:AReview

KristinaKlabenkova1,2,AlesyaFokina1,2,*andDmitryStetsenko1,2

1FacultyofPhysics,NovosibirskStateUniversity,630090Novosibirsk,Russia;k.klabenkova@g.nsu.ru(K.K.);

d.stetsenko@nsu.ru(D.S.)

2InstituteofCytologyandGenetics,RussianAcademyofSciences,SiberianBranch,

630090Novosibirsk,Russia

*Correspondence:a.fokina@nsu.ru;Tel.:+7-383-363-4963

Abstract:Peptide-oligonucleotideconjugates(POCs)representoneoftheincreasinglysuccessful

albeitcostlyapproachestoincreasingthecellularuptake,tissuedelivery,bioavailability,and,thus,

overallefficiencyoftherapeuticnucleicacids,suchas,antisenseoligonucleotidesandsmallinter-

feringRNAs.ThisreviewputsthesubjectofchemicalsynthesisofPOCsintothewidercontextof

therapeuticoligonucleotidesandtheproblemofnucleicaciddrugdelivery,cell-penetratingpep-

tidestructuraltypes,themechanismsoftheirintracellulartransport,andthewaysofapplication,

whichincludetheformationofnon-covalentcomplexeswitholigonucleotides(peptideadditives)

orcovalentconjugation.ThemainstrategiesforthesynthesisofPOCsareviewedindetail,which

areconceptuallydividedinto(a)thestepwisesolid-phasesynthesisapproachand(b)post-synthetic

conjugationeitherinso