Molecules often take advantage of cyclic topology to enable enhancement of their properties such as thermal stability, binding affinity to targets, and self-assembly profiles. Despite the advantages of cyclization, peptide-oligonucleotide conjugates (POCs) have not fully utilized the cyclic topology, presumably due to a dearth of generalized synthetic methods. Here, we report a feasible way to synthesize self-assembling cyclic POCs using a thiol-maleimide reaction and copper-catalyzed azide-alkyne cycloaddition (CuAAC) in the solution phase and evaluate the properties of cyclic POCs such as molecular conformation, Watson-Crick base pairing, and self-assembly profile in comparison to those of linear POCs. Although there is a marginal difference between cyclic POCs and linear POCs in terms of their overall conformation, the self-assembly profile is greatly affected. The cyclic POCs form homogeneous spherical aggregates, while the linear POCs form a heterogeneous population of fibrous and spherical aggregates. On the other hand, these cyclic POCs show less efficiency in Watson-Crick base pairing to complementary cyclic POCs than linear POCs, which subsequently affects the self-assembly of each duplex POC. Our study provides a synthetic method for self-assembling cyclic POCs as well as a better understanding of the effect of cyclic topology on the overall conformation, self-assembly, and Watson-Crick base pairing of POCs.
Bibliographical noteFunding Information:
This work was supported by grants from the National Research Foundation (NRF) of Korea (2020R1A2C2007578).
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All Science Journal Classification (ASJC) codes
- Organic Chemistry