Geron Files new patent: Synthesis of protected 3'-amino nucleoside monomers
Posted: Sun Dec 18, 2016 10:17 pm
USPTO Applicaton #: #20160362440
Applicant: Geron Corporation
Inventors: Sergei M. Gryaznov, Krisztina Pongracz, Daria Zielinska
Date: 12/15/16
Abstract
Orthogonally protected 3′-amino nucleoside monomers and efficient methods for their synthesis are described. The methods employ selective protection of the 3′-amino group in the presence of the unprotected nucleoside base.
Background of the invention
The use of oligonucleotides and oligonucleotide analogs as therapeutic agents, based on specific binding to target nucleic acid sequences or to proteins, has been extensively researched. Structurally modified oligonucleotide analogs have been designed which lack the nuclease susceptibility of natural (phosphodiester-linked) oligonucleotides and which, in some cases, exhibit other beneficial properties such as enhanced binding to targets or enhanced specificity of binding. One such class of oligonucleotide analog is the N3'.fwdarw.P5' phosphorodiamidate-linked oligonucleotide (Gryaznov and Chen, 1994; Chen et al., 1994). These compounds are nuclease resistant, form stable duplexes with complementary RNA and duplex DNA targets, and have demonstrated significant sequence-specific antisense activity both in vitro and in vivo (Gryaznov et al., 1995; Escude et al., 1996; Gryaznov et al., 1996; Giovannangeli et al., 1997; Skorski et al., 1997).
Claim
A method of preparing an adenosine, guanosine or cytidine monomer having a protected nucleoside base and a protected 3'-amino group, wherein said base and said 3'-amino group are orthogonally protected, the method comprising: (a) providing a 3'-amino-3'-deoxy adenosine, cytidine, or guanosine monomer in which the 5'-hydroxyl group, nucleoside base, and 3'-amino group are unprotected; (b) selectively reacting said 3'-amino group with a first protecting group; reacting said 5'-hydroxyl group with a second protecting group; and reacting said nucleoside base with a third protecting group; wherein said first protecting group can be removed from said 3'-amino group under conditions which do not deprotect said nucleoside base, and said second protecting group can be removed from said 5'-hydroxyl group under conditions which do not deprotect said nucleoside base or said 3'-amino group.
Link: http://appft.uspto.gov/netacgi/nph-Pars ... 0160362440
Applicant: Geron Corporation
Inventors: Sergei M. Gryaznov, Krisztina Pongracz, Daria Zielinska
Date: 12/15/16
Abstract
Orthogonally protected 3′-amino nucleoside monomers and efficient methods for their synthesis are described. The methods employ selective protection of the 3′-amino group in the presence of the unprotected nucleoside base.
Background of the invention
The use of oligonucleotides and oligonucleotide analogs as therapeutic agents, based on specific binding to target nucleic acid sequences or to proteins, has been extensively researched. Structurally modified oligonucleotide analogs have been designed which lack the nuclease susceptibility of natural (phosphodiester-linked) oligonucleotides and which, in some cases, exhibit other beneficial properties such as enhanced binding to targets or enhanced specificity of binding. One such class of oligonucleotide analog is the N3'.fwdarw.P5' phosphorodiamidate-linked oligonucleotide (Gryaznov and Chen, 1994; Chen et al., 1994). These compounds are nuclease resistant, form stable duplexes with complementary RNA and duplex DNA targets, and have demonstrated significant sequence-specific antisense activity both in vitro and in vivo (Gryaznov et al., 1995; Escude et al., 1996; Gryaznov et al., 1996; Giovannangeli et al., 1997; Skorski et al., 1997).
Claim
A method of preparing an adenosine, guanosine or cytidine monomer having a protected nucleoside base and a protected 3'-amino group, wherein said base and said 3'-amino group are orthogonally protected, the method comprising: (a) providing a 3'-amino-3'-deoxy adenosine, cytidine, or guanosine monomer in which the 5'-hydroxyl group, nucleoside base, and 3'-amino group are unprotected; (b) selectively reacting said 3'-amino group with a first protecting group; reacting said 5'-hydroxyl group with a second protecting group; and reacting said nucleoside base with a third protecting group; wherein said first protecting group can be removed from said 3'-amino group under conditions which do not deprotect said nucleoside base, and said second protecting group can be removed from said 5'-hydroxyl group under conditions which do not deprotect said nucleoside base or said 3'-amino group.
Link: http://appft.uspto.gov/netacgi/nph-Pars ... 0160362440