Development of a nucleoside analog UV light sensor

Article abstract of DOI:10.1081/NCN-120022614

Conjugation of the photosensitive nucleoside (E)-5-(2-methoxycarbonylethenyl)-cytidine to biotin provided a means to attach this analogue to microparticles for dosimetry applications that require uv sensor mobility.

Full text of DOI:10.1081/NCN-120022614

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Nucleosides, Nucleotides and Nucleic Acids
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Development of a Nucleoside Analog UV Light Sensor
Shiyue Fang a c , Yousheng Guan a , Ernest R. Blatchley III b , Lian-Shin Lin b , Cheng Yue Shen
b & Donald E. Bergstrom a c d
a Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West
Lafayette, Indiana, USA
b School of Civil Engineering, Purdue University, West Lafayette, Indiana, USA
c Walther Cancer Institute, Indianapolis, Indiana, USA
d Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, 401,
Hansen Building, West Lafayette, IN, 47907-1333, USA
Published online: 31 Aug 2006.
To cite this article: Shiyue Fang , Yousheng Guan , Ernest R. Blatchley III , Lian-Shin Lin , Cheng Yue Shen & Donald E.
Bergstrom (2003) Development of a Nucleoside Analog UV Light Sensor, Nucleosides, Nucleotides and Nucleic Acids, 22:5-8,
703-705, DOI: 10.1081/NCN-120022614
To link to this article: http://dx.doi.org/10.1081/NCN-120022614
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NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS
Vol. 22, Nos. 5–8, pp. 703–705, 2003
Development of a Nucleoside Analog UV Light Sensor
Shiyue Fang,1,3 Yousheng Guan,1 Ernest R. Blatchley III,2 Lian-Shin Lin,2
Cheng Yue Shen,2 and Donald E. Bergstrom1,3,
*
1Department of Medicinal Chemistry and Molecular Pharmacology and
2School of Civil Engineering, Purdue University, West Lafayette,
Indiana, USA
3Walther Cancer Institute, Indianapolis, Indiana, USA
ABSTRACT
Conjugation of the photosensitive nucleoside (E)-5-(2-methoxycarbonylethenyl)-
cytidine to biotin provided a means to attach this analogue to microparticles
for dosimetry applications that require uv sensor mobility.
Key Words: Biotin; Nucleoside; Photosensor; Fluorescence.
The nucleoside analog (E)-5-(2-methoxycarbonylethenyl) cytidine (1) undergoes
photon mediated isomerization to the Z-isomer, which rapidly ring closes to the
highly fluorescent 3-b-D-ribofuranosyl-2,7-dioxopyrido[2,3-d]pyrimidine, 2.[1] We
were interested in exploiting this photo-mediated reaction to develop sensors for
applications requiring in-situ uv-light dosimetry. This required finding a way to
*Correspondence: Donald E. Bergstrom, Department of Medicinal Chemistry and Molecular
Pharmacology, Purdue University, 401, Hansen Building, West Lafayette, IN 47907-1333,
USA; Fax: þ 1 765 494 9193; E-mail: bergstrom@purdue.com.
703
DOI: 10.1081/NCN-120022614
Copyright # 2003 by Marcel Dekker, Inc.
1525-7770 (Print); 1532-2335 (Online)
www.dekker.com

704
Fang et al.
conjugate nucleoside 1 to biomolecules and
microparticles that would not interfere with the uv-mediated reaction. To accom-
plish this goal we chose to link biotin to nucleoside 1. Biotin can irreversibly bind
to streptavidin via a non-covalent interaction by simple incubation in buffer at room
temperature, and a variety of streptavidin functionalized solid microspheres are
Scheme 1. Reagents and conditions: i. MeMgBr, THF, ꢀ78ꢁC to 50ꢁC, overnight. ii. AcOH,
water, 12 h. iii. 2,20-(Ethylenedioxy)bis(ethylamine), water, 90ꢁC, overnight. iv. Isobutyl chloro-
formate, DMF, Et3N, biotin; then 5. v. iPr2SiCl2, DMF, Py, ꢀ60ꢁC to RT, 5h. vi. 20,30-Isopro-
pylidene derivative of 1 in DMF, Py, ꢀ60ꢁC to RT, 12 h.
Figure 1. Dose response as a function of initial beads concentrations (Beads=L).

Nucleoside Analog UV Light Sensor
705
commercially available. The combination of functional groups on nucleoside 1 pre-
sented a significant synthetic challenge for conjugation to biotin. To accomplish this
we synthesized nucleoside 7 (Sch. 1) in which the key structural feature is a stable
silicon linkage. Nucleoside 7 was a single diastereomer and proved easy to purify
and stable in water because of the tertiary alcohol linkage to the silicon.
Incubation of 7 with streptavidin coated beads (ꢂ5 mm in diameter, Bangs
Laboratories, Inc.) in TTL buffer for 20 min at room temperature yielded derivatized
beads whose fluorescence, when suspended in water, increased proportionally to uv
dose (Fig. 1). The fluorescence was measured using a fluorescence spectrophotometer
at 385 nm excited at 330 nm. Attachment of nucleoside 7 to streptavadin coated
magnetic microparticles, which would allow retrieval from complex systems, is under
investigation.
ACKNOWLEDGMENTS
Grant support from the National Institutes of Health (GM53155) and the
Showalter Trust Fund and assistance from the National Cancer Institute Grant
(P30 CA23168) awarded to Purdue University are gratefully acknowledged.
REFERENCE
1. Bergstrom, D.E.; Inoue, H.; Reddy, P.A. Pyrido[2,3-d]pyrimidine nucleosides.
Synthesis via cyclization of C-5 substituted cytidines. J. Org. Chem. 1982, 47,
2174–2178.