Computational and NMR spectroscopy insights into the conformation of cyclic di-nucleotides.
Sci Rep
; 7(1): 16550, 2017 11 29.
Article
in En
| MEDLINE
| ID: mdl-29185472
ABSTRACT
Cyclic di-nucleotides (CDNs) are second messengers in bacteria and metazoan that are as such controlling important biological processes. Here the conformational space of CDNs was explored systematically by a combination of extensive conformational search and DFT calculations as well as NMR methods. We found that CDNs adopt pre-organized conformations in solution in which the ribose conformations are North type and glycosidic bond conformations are anti type. The overall flexibility of CDNs as well as the backbone torsion angles depend on the cyclization of the phosphodiester bond. Compared to di-nucleotides, CDNs display high rigidity in the macrocyclic moieties. Structural comparison studies demonstrate that the pre-organized conformations of CDNs highly resemble the biologically active conformations. These findings provide information for the design of small molecules to modulate CDNs signalling pathways in bacteria or as vaccine adjuvants. The rigidity of the backbone of CDNs enables the design of high order structures such as molecular cages based on CDNs analogues.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Magnetic Resonance Spectroscopy
/
Nucleotides, Cyclic
Language:
En
Journal:
Sci Rep
Year:
2017
Document type:
Article
Affiliation country: