Cleavable dna-encoded library

A compound used as a head piece of a compound library, which is a compound represented by the formula (I)

• wherein
• E and F are each independently
• an oligomer constituted by nucleotides or nucleic acid analogues,
• provided that E and F contain base sequences, which are complementary to each other and form a duplex oligonucleotide,
• LP is a loop site,
• L is a linker and
• D is a reactive functional group and
• has at least one selectively cleavable site at any of at least one site of E, F and LP.

A compound used as a head piece of a DNA-encoded library, which is a compound represented by the formula (I)

• wherein
• E and F are each independently
• an oligomer constituted by nucleotides or nucleic acid analogues,
• provided that E and F contain base sequences, which are complementary to each other and form a duplex oligonucleotide,
• LP is a loop site,
• L is a linker and
• D is a reactive functional group and
• has at least one selectively cleavable site at any of at least one site of E, F and LP.

A head piece of a compound library, which is a compound represented by the formula (I)

• wherein
• E and F are each independently
• an oligomer constituted by nucleotides or nucleic acid analogues,
• provided that E and F contain base sequences, which are complementary to each other and form a duplex oligonucleotide,
• LP is a loop site,
• L is a linker and
• D is a reactive functional group and
• has at least one selectively cleavable site at any of at least one site of E, F and LP.

A head piece of a DNA-encoded library, which is a compound represented by the formula (I)

• wherein
• E and F are each independently
• an oligomer constituted by nucleotides or nucleic acid analogues,
• provided that E and F contain base sequences, which are complementary to each other and form a duplex oligonucleotide,
• LP is a loop site,
• L is a linker and
• D is a reactive functional group and
• has at least one selectively cleavable site at any of at least one site of E, F and LP.

A compound represented by the formula (II)

• wherein
• X and Y are oligonucleotide chains,
• E and F are each independently
• an oligomer constituted by nucleotides or nucleic acid analogues,
• provided that E and F contain base sequences, which are complementary to each other and form a duplex oligonucleotide,
• LP is a loop site,
• L is a linker and
• D is a divalent group derived from a reactive functional group,
• Sp is a bonding or a bifunctional spacer and
• An is a partial structure constituted by at least one building block,
• X and Y have a sequence capable of forming a duplex at least a part thereof,
• X binds to E at the 5′ terminal end,
• Y binds to F at the 3′ terminal end and
• has at least one selectively cleavable site at any of at least one site of E, F and LP.

A method which is a method for producing a compound An-Sp-C-Bn,

• An is a partial structure constructed by n building blocks α1 to αn and n is an integer of 2 to 10,
• Sp is a bond or a bifunctional spacer,
• C is a hairpin type head piece having at least one “selectively cleavable site” and
• Bn is a partial structure containing an oligonucleotide which contains a base sequence capable of identifying the structure of An,
• which comprises subjecting to C the following steps of;
• (a) binding α1-Sp, or binding Sp and α1 and
• (b) binding an oligonucletide tag which contains a base sequence capable of identifying a structure of α1,
• to obtain a compound A1-Sp-C—B1,
• then, subjecting to A(m−1)-Sp-C—B(m−1), where m is an integer of 2 to n,
• the following steps (c) and (d) by repeating until m from 2 to n in ascending order;
• (c) binding αn to the A portion and
• (d) binding an oligonucletide tag which contains a base sequence capable of identifying a structure of αn to the B portion
• to obtain a compound Am-Sp-C-Bm,
• where the steps (a) and (b) and the steps (c) and (d) can be carried out in an optional order.

A method which is a method for evaluating a compound library containing at least one compound represented by the formula (III)

• An-Sp-C-Bn (III)
• wherein
• An is a partial structure constructed by n building blocks α1 to αn and n is an integer of 1 to 10,
• Sp is a bonding or a bifunctional spacer and
• C is a hairpin type head piece having at least one “selectively cleavable site” and
• Bn is a partial structure containing an oligonucleotide which contains a base sequence capable of identifying the structure of An,
• which is constituted by the following steps of:
• (1) by contacting the compound library with a biological target under conditions suitable for binding at least one library molecule of the compound library to the target,
• (2) removing the library molecule that does not bind to the target and selecting a library molecule that have affinity to the biological target,
• (3) cleaving cleavable sites selectively,
• (4) identifying sequences of oligonucleotides constituting Bn and
• (5) using the sequences determined in (4) to identify the structure of one or more compounds that bind to the biological target.