Conformational diversity in contryphans from conus venom: Cis-trans isomerisation and aromatic/proline interactions in the 23-membered ring of a 7-residue peptide disulfide loop
View/Open
15175_ftp.pdf (2,182Mb) (Restricted access)
Request copy
Què és aquest botó?
Aquest botó permet demanar una còpia d'un document restringit a l'autor. Es mostra quan:
- Disposem del correu electrònic de l'autor
- El document té una mida inferior a 20 Mb
- Es tracta d'un document d'accés restringit per decisió de l'autor o d'un document d'accés restringit per política de l'editorial
Cita com:
hdl:2117/21326
Document typeArticle
Defense date2013-11-05
Rights accessRestricted access - publisher's policy
Except where otherwise noted, content on this work
is licensed under a Creative Commons license
:
Attribution-NonCommercial-NoDerivs 3.0 Spain
Abstract
Conformational diversity or
“shapeshifting” in cyclic peptide natu-
ral products can, in principle, confer a
single molecular entity with the proper-
ty of binding to multiple receptors.
Conformational equilibria have been
probed in the contryphans, which are
peptides derived from
Conus
venom
possessing a 23-membered cyclic disul-
fide moiety. The natural sequences
derived from
Conus inscriptus
,
GCV
D
LYPWC* (In936) and
Conus lor-
oisii
, GCP
D
WDPWC* (Lo959) differ in
the number of proline residues within
the macrocyclic ring. Structural charac-
terisation of distinct conformational
states arising from
cis
–
trans
equilibria
about Xxx–Pro bonds is reported. Iso-
merisation about the C2–P3 bond is
observed in the case of Lo959 and
about the Y5–P6 bond in In936. Evi-
dence is presented for as many as four
distinct species in the case of the syn-
thetic analogue V3P In936. The Tyr-
Pro-Trp segment in In936 is character-
ised by distinct sidechain orientations
as a consequence of aromatic/proline
interactions as evidenced by specific
sidechain–sidechain nuclear Overhaus-
er effects and ring current shifted
proton chemical shifts. Molecular dy-
namics simulations suggest that Tyr5
and Trp7 sidechain conformations are
correlated and depend on the geometry
of the Xxx–Pro bond. Thermodynamic
parameters are derived for the
cis
$
trans
equilibrium for In936. Studies on
synthetic analogues provide insights
into the role of sequence effects in
modulating isomerisation about Xxx–
Pro bonds.
CitationSonti, R. [et al.]. Conformational diversity in contryphans from conus venom: Cis-trans isomerisation and aromatic/proline interactions in the 23-membered ring of a 7-residue peptide disulfide loop. "Chemistry: a european journal", 05 Novembre 2013, vol. 19, núm. 45, p. 15175-15189.
ISSN0947-6539
Files | Description | Size | Format | View |
---|---|---|---|---|
15175_ftp.pdf![]() | 2,182Mb | Restricted access |