Molecular spacer arm, process for the production thereof and uses on an analytical chip comprising molecules or biomolecules

Molecular spacer arm of formula (I) below:

• wherein X0 and X4 are substitutents which can be modulated so as to allow bonding of [mo] and [Sup] via said spacer arm, X0 and X4 being different from H and each being chosen, independently of the other substitutents of the spacer arm, from C, O, N, S, Se, P, As and Si;
• and
• wherein the substitutents X1, X2, X1, Z1, Z2, R1, R2, and R3 are such that:
• X1, X2, and X3 are each chosen, independently of the other substitutents, from C, O, N, S, Se, P, As and Si, and from an aryl and a heteroaryl, each containing from 2 to 20 carbon atoms;
• Z1 and Z2 are each chosen, independently of the other substitutents, from C—R, Si—R, C, N, P and As, where R is an alkyl containing from 1 to 40 carbon atoms;
• R1, R2, and R3 are each chosen, independently of the other substitutents, from H, an alkyl, an aryl and a heteroaryl each containing from 2 to 20 carbon atoms;
• [Gp] represents a group which protects the secondary amine —N— or a molecule which participates in the functionality of the spacer arm;
• wherein n, m and p are integers, each greater than or equal to 1 and chosen independently of one another;
• wherein [Sup] represents H or a silanized solid support;
• and
• wherein [mo] represents H or a molecular unit.

A process for attaching a molecular unit [mo] to a silanized solid support [Sup] comprising covalently attaching the molecular unit to the silanized solid support through a molecular spacer arm according to formula (I):

• wherein X0 and X4 are substitutents which can be modulated so as to allow bonding of [mo] and [Sup] via said spacer arm, X0 and X4 being different from H and each being chosen, independently of the other substitutents of the spacer arm, from C, O, N, S, Se, P, As and Si;
• and
• wherein the substitutents X1, X1, X3, Z1, Z2, R1, R2, and R3 are such that:
• X1, X2, and X3 are each chosen, independently of the other substitutents, from C, O, N, S, Se, P, As and Si, and from an aryl and a heteroaryl, each containing from 2 to 20 carbon atoms;
• Z1 and Z2 are each chosen, independently of the other substitutents, from C—R, Si—R, C, N, P and As, where R is an alkyl containing from 1 to 40 carbon atoms;
• R1, R2, and R3 are each chosen, independently of the other substitutents, from H, an alkyl, an aryl and a heteroaryl each containing from 2 to 20 carbon atoms;
• [Gp] represents a group which protects the secondary amine —N— or a molecule which participates in the functionality of the spacer arm;
• and
• wherein n, m and p are integers, each greater than or equal to 1 and chosen independently of one another.

A process for producing a biochip comprising attaching a molecular unit [mo] to a silanized solid support [Sup], by a process comprising covalently attaching the molecular unit to the silanized solid support through a molecular spacer arm according to formula (I):

• wherein X0 and X4 are substitutents which can be modulated so as to allow bonding of [mo] and [Sup] via said spacer arm, X0 and X4 being different from H and each being chosen, independently of the other substitutents of the spacer arm, from C, O, N, S, Se, P, As and Si;
• and
• wherein the substitutents X1, X2, X3, Z1, Z2, R1, R2, and R3 are such that:
• X1, X2, and X3 are each chosen, independently of the other substitutents, from C, O, N, S, Se, P, As and Si, and from an aryl and a heteroaryl, each containing from 2 to 20 carbon atoms;
• Z1 and Z2 are each chosen, independently of the other substitutents, from C—R, Si—R, C, N, P and As, where R is an alkyl containing from 1 to 40 carbon atoms;
• R1, R2, and R3 are each chosen, independently of the other substitutents, from H, an alkyl, an aryl and a heteroaryl each containing from 2 to 20 carbon atoms;
• [Gp] represents a group which protects the secondary amine —N— or a molecule which participates in the functionality of the spacer arm;
• and
• wherein n, m and p are integers, each greater than or equal to 1 and chosen independently of one another.

A process for producing a glycochip comprising attaching a molecular unit [mo] to a silanized solid support [Sup] by a process comprising covalently attaching the molecular unit to the silanized solid support through a molecular spacer arm according to formula (I):

• wherein X0 and X4 are substitutents which can be modulated so as to allow bonding of [mo] and [Sup] via said spacer arm, X0 and X4 being different from H and each being chosen, independently of the other substitutents of the spacer arm, from C, O, N, S, Se, P, As and Si;
• and
• wherein the substitutents X1, X2, X3, Z1, Z2, R1, R2, and R3 are such that:
• X1, X2, and X3 are each chosen, independently of the other substitutents, from C, O, N, S, Se, P, As and Si, and from an aryl and a heteroaryl, each containing from 2 to 20 carbon atoms;
• Z1 and Z2 are each chosen, independently of the other substitutents, from C—R, Si—R, C, N, P and As, where R is an alkyl containing from 1 to 40 carbon atoms;
• R1, R2, and R3 are each chosen, independently of the other substitutents, from H, an alkyl, an aryl and a heteroaryl each containing from 2 to 20 carbon atoms;
• [Gp] represents a group which protects the secondary amine —N— or a molecule which participates in the functionality of the spacer arm;
• and
• wherein n, m and p are integers, each greater than or equal to 1 and chosen independently of one another.

Process for the covalent attachment of a molecular unit [mo] to a support by means of a spacer arm, said process comprising the following steps:

• (i) reduction of the nitrile function of a compound of formula:
• (ii) formation of an aldehyde function from an allyl function of a biological molecule of formula:
• (iii) reductive amination, followed by protection of the secondary amine formed, between said reduced nitrile function and said aldehyde function, so as to obtain a biological molecule which has been activated so as to be attached to the support, said activated biological molecule being of formula:
• (iv) silanization of a solid support, and functionalization of the silanized solid support with a molecule of formula:
• (v) metathesis reaction between the molecule functionalizing the support and the activated biological molecule so as to form a spacer arm connecting the biological molecule and the support;
• wherein X0 and X4 are substitutents which can be modulated so as to allow bonding of [mo] and the support via said spacer arm, X0 and X4 being different from H and each being chosen, independently of the other substitutents of the spacer arm, from C, O, N, S, Se, P, As and Si;
• and
• wherein the substitutents X1, X2, X3, Z1, Z2, R1, R2, and R3 are such that:
• X1, X2, and X3 are each chosen, independently of the other substitutents, from C, O, N, S, Se, P, As and Si, and from an aryl and a heteroaryl, each containing from 2 to 20 carbon atoms;
• Z1 and Z2 are each chosen, independently of the other substitutents, from C—R, Si—R, C, N, P and As, where R is an alkyl containing from 1 to 40 carbon atoms;
• R1, R2, and R3 are each chosen, independently of the other substitutents, from H, an alkyl, an aryl and a heteroaryl each containing from 2 to 20 carbon atoms;
• [Gp] represents a group which protects the secondary amine —N— or a molecule which participates in the functionality of the spacer arm;
• and
• wherein n, m and p are integers, each greater than or equal to 1 and chosen independently of one another.

A process for producing a biochip comprising covalently attaching a molecular unit [mo] to a support by means of a spacer arm by the following steps:

• (i) reduction of the nitrile function of a compound of formula:
• (ii) formation of an aldehyde function from an allyl function of a biological molecule of formula:
• (iii) reductive amination, followed by protection of the secondary amine formed, between said reduced nitrile function and said aldehyde function, so as to obtain a biological molecule which has been activated so as to be attached to the support, said activated biological molecule being of formula:
• (iv) silanization of a solid support, and functionalization of the silanized solid support with a molecule of formula:
• (v) metathesis reaction between the molecule functionalizing the support and the activated biological molecule so as to form a spacer arm connecting the biological molecule and the support;
• wherein X0 and X4 are substitutents which can be modulated so as to allow bonding of [mo] and the support via said spacer arm, X0 and X4 being different from H and each being chosen, independently of the other substitutents of the spacer arm, from C, O, N, S, Se, P, As and Si;
• and
• wherein the substitutents X1, X2, X3, Z1, Z2, R1, R2, and R3 are such that:
• X1, X2, and X3 are each chosen, independently of the other substitutents, from C, O, N, S, Se, P, As and Si, and from an aryl and a heteroaryl, each containing from 2 to 20 carbon atoms;
• Z1 and Z2 are each chosen, independently of the other substitutents, from C—R, Si—R, C, N, P and As, where R is an alkyl containing from 1 to 40 carbon atoms;
• R1, R2, and R3 are each chosen, independently of the other substitutents, from H, an alkyl, an aryl and a heteroaryl each containing from 2 to 20 carbon atoms;
• [Gp] represents a group which protects the secondary amine —N— or a molecule which participates in the functionality of the spacer arm;
• and
• wherein n, m and p are integers, each greater than or equal to 1 and chosen independently of one another.

A process for producing a glycochip comprising covalently attaching a molecular unit [mo] to a support by means of a spacer arm the following steps:

• (i) reduction of the nitrile function of a compound of formula:
• (ii) formation of an aldehyde function from an allyl function of a biological molecule of formula:
• (iii) reductive amination, followed by protection of the secondary amine formed, between said reduced nitrile function and said aldehyde function, so as to obtain a biological molecule which has been activated so as to be attached to the support, said activated biological molecule being of formula:
• (iv) silanization of a solid support, and functionalization of the silanized solid support with a molecule of formula:
• (v) metathesis reaction between the molecule functionalizing the support and the activated biological molecule so as to form a spacer arm connecting the biological molecule and the support;
• wherein X0 and X4 are substitutents which can be modulated so as to allow bonding of [mo] and the support via said spacer arm, X0 and X4 being different from H and each being chosen, independently of the other substitutents of the spacer arm, from C, O, N, S, Se, P, As and Si;
• and
• wherein the substitutents X1, X2, X3, Z1, Z2, R1, R2, and R3 are such that:
• X1, X2, and X3 are each chosen, independently of the other substitutents, from C, O, N, S, Se, P, As and Si, and from an aryl and a heteroaryl, each containing from 2 to 20 carbon atoms;
• Z1 and Z2 are each chosen, independently of the other substitutents, from C—R, Si—R, C, N, P and As, where R is an alkyl containing from 1 to 40 carbon atoms;
• R1, R2, and R3 are each chosen, independently of the other substitutents, from H, an alkyl, an aryl and a heteroaryl each containing from 2 to 20 carbon atoms;
• [Gp] represents a group which protects the secondary amine —N— or a molecule which participates in the functionality of the spacer arm;
• and
• wherein n, m and p are integers, each greater than or equal to 1 and chosen independently of one another.