Method for the synthesis of a bifunctional complex
First Claim
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1. A method for the synthesis of a library of different bifunctional complexes, each comprising a molecule part and a double stranded oligonucleotide coding part identifying the molecule part, said method comprising the steps ofi) providing a scaffold “
- X”
linked to an oligonucleotide “
x”
, wherein the oligonucleotide “
x”
is capable of functioning as an identifier for scaffold “
X”
in a plurality of different reaction compartments;
ii) providing a plurality of different reactants “
A”
;
iii) providing a plurality of different oligonucleotides “
a”
, wherein the different oligonucleotides “
a”
are capable of functioning as identifiers for the different reactants “
A”
;
iv) reacting a different reactant “
A”
from step (ii) with scaffold “
X”
in each of the different reaction compartments, thereby generating a plurality of different molecule parts “
XA”
;
v) connecting a different oligonucleotide “
a”
from step (iii) with oligonucleotide “
x”
by chemical or enzymatic ligation in each of the different reaction compartments, thereby generating a plurality of different oligonucleotide coding parts comprising “
xa” and
identifying “
XA”
; and
vi) making the plurality of different oligonucleotide coding parts comprising “
xa”
double stranded by a process comprising a polymerase extension reactionwherein the molecule parts “
XA”
are small, non-polymeric molecules with a molecular weight of less than 1000 Da.
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Abstract
Disclosed is a method for obtaining a bifunctional complex comprising a display molecule part and a coding part, wherein a nascent bifunctional complex comprising a chemical reaction site and a priming site for enzymatic addition of a tag is reacted at the chemical reaction site with one or more reactants, and provided with respective tag(s) identifying the reactant(s) at the priming site is using one or more enzymes.
147 Citations
52 Claims
-
1. A method for the synthesis of a library of different bifunctional complexes, each comprising a molecule part and a double stranded oligonucleotide coding part identifying the molecule part, said method comprising the steps of
i) providing a scaffold “ - X”
linked to an oligonucleotide “
x”
, wherein the oligonucleotide “
x”
is capable of functioning as an identifier for scaffold “
X”
in a plurality of different reaction compartments;ii) providing a plurality of different reactants “
A”
;iii) providing a plurality of different oligonucleotides “
a”
, wherein the different oligonucleotides “
a”
are capable of functioning as identifiers for the different reactants “
A”
;iv) reacting a different reactant “
A”
from step (ii) with scaffold “
X”
in each of the different reaction compartments, thereby generating a plurality of different molecule parts “
XA”
;v) connecting a different oligonucleotide “
a”
from step (iii) with oligonucleotide “
x”
by chemical or enzymatic ligation in each of the different reaction compartments, thereby generating a plurality of different oligonucleotide coding parts comprising “
xa” and
identifying “
XA”
; andvi) making the plurality of different oligonucleotide coding parts comprising “
xa”
double stranded by a process comprising a polymerase extension reactionwherein the molecule parts “
XA”
are small, non-polymeric molecules with a molecular weight of less than 1000 Da. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 48, 49, 50, 51, 52)
- X”
-
37. A method for alternating, parallel synthesis of a combinatorial library comprising different bifunctional complexes, each bifunctional complex comprising a molecule part and a double stranded oligonucleotide coding part identifying the molecule part, said method comprising the steps of
i) providing a scaffold “ - X”
linked to an oligonucleotide “
x”
, wherein the oligonucleotide “
x”
is capable of functioning as an identifier for scaffold “
X”
in each of a plurality of different reaction compartments;ii) providing a plurality of different reactants; iii) providing a plurality of different oligonucleotides, wherein each different oligonucleotide is capable of functioning as an identifier for a different reactant; iv) reacting a different reactant from step (ii) with scaffold “
X”
in each different reaction compartment, thereby generating different molecule parts;v) connecting oligonucleotide “
x”
with a different oligonucleotide from step iii) in each different reaction compartment, thereby generating different oligonucleotide coding parts comprising oligonucleotide “
x”
; andvi) making the different oligonucleotide coding parts comprising oligonucleotide “
x”
double stranded by a process comprising a polymerase extension reactionwherein the different molecule parts are small, non-polymeric molecules with a molecular weight of less than 1000 Da. - View Dependent Claims (38, 39, 40, 41, 42, 43, 44, 45, 46, 47)
- X”
Specification