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Double-clicking peptides onto phosphorothioate oligonucleotides: combining two proapoptotic agents in one molecule.
- Source :
-
Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2014 Sep 22; Vol. 53 (39), pp. 10504-9. Date of Electronic Publication: 2014 Aug 19. - Publication Year :
- 2014
-
Abstract
- Described here is a method for the conjugation of phosphorothioate oligonucleotides (PSOs) with peptides. PSOs are key to antisense technology. Peptide-PSO conjugates may improve target specificity, tissue distribution, and cellular uptake of PSOs. However, the highly nucleophilic phosphorothioate structure poses a challenge to conjugation chemistry. Herein, we introduce a new method which involves a sequence of oxime ligation and strain-promoted [2+3] cycloaddition. The usefulness of the method was demonstrated in the synthesis of peptide-PSO conjugates that targeted two suppressors of both the intrinsic and the extrinsic pathway of apoptosis. It is shown that the activity of a PSO sequence targeted against mRNA from c-Flip can be enhanced by conjugation with a peptide mimetic designed to inhibit the X-linked inhibitor of apoptosis protein (XIAP).<br /> (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Subjects :
- Amino Acid Sequence
Antineoplastic Agents chemical synthesis
Antineoplastic Agents toxicity
Base Sequence
CASP8 and FADD-Like Apoptosis Regulating Protein genetics
Cell Line, Tumor
Cell Survival drug effects
Cycloaddition Reaction
Humans
Oximes chemistry
RNA, Messenger chemistry
X-Linked Inhibitor of Apoptosis Protein chemistry
Antineoplastic Agents chemistry
Oligonucleotides, Antisense chemistry
Peptides chemistry
Phosphates chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1521-3773
- Volume :
- 53
- Issue :
- 39
- Database :
- MEDLINE
- Journal :
- Angewandte Chemie (International ed. in English)
- Publication Type :
- Academic Journal
- Accession number :
- 25138283
- Full Text :
- https://doi.org/10.1002/anie.201406674