Cellular recognition conjugates and methods of use for the histological analysis of cancer tissue using MALDI-MS imaging
AssigneeGeorgia State University Research Foundation, Inc.
InventorsChaofeng Dai, Binghe Wang, Lifang Wang, Yong Chu
Life of this patent
Estimating the term…
Abstract
Disclosed are conjugates that can bind to one or more site on cancer cell surface, for example, surface proteins, compound specific receptors and carbohydrates that comprise the surface of specific cell types. The disclosed conjugates can thereby serve as indicators identifying the presence of cancerous tissue.
Claims19
An imaging agent having the formula:
- wherein X is chosen from:
- each L1 is independently chosen from:
- i) —(CH2)yC(O)O(CH2)z—;
- ii) —(CH2)yOC(O)(CH2)z—;
- iii) —(CH2)yC(O)NR6(CH2)z—;
- iv) —(CH2)yNR6C(O)(CH2)z—;
- v) —(CH2)yNR6C(O)NH(CH2)z—;
- or
- vi) —(CH2)yNR6C(NR6)NR6(CH2)z—;
- R6 is hydrogen or C1-C3 linear alkyl;
- the index y is an integer from 0 to 4, the index z is an integer form 0 to 4;
- R has the formula:
- the index k is an integer from 1 to 5;
- L2 has the formula:
- i) (CH2)pNR7(CH2)q;
- or
- ii) (CH2)pO(CH2)q;
- R7 is hydrogen or C1-C3 linear alkyl;
- the index p is an integer from 0 to 5;
- the index q is an integer from 0 to 5;
- Z has the formula:
- R1 an R2 are substituted or unsubstituted aryl groups chosen from phenyl, naphthyl, anthracenyl, phenanthrenyl, or tetracenyl;
- R3 is a substituted or unsubstituted aryl group chosen from phenyl, naphthyl, anthracenyl, phenanthrenyl, or tetracenyl, and wherein R3 further comprises an anchoring group having the formula:
- wherein Q is a unit having the formula:
- i) —(CH2)rC(O)O(CH2)tR9;
- ii) —(CH2)rOC(O)(CH2)tR9;
- iii) —(CH2)rC(O)NR8(CH2)tR9;
- iv) —(CH2)rNR8C(O)(CH2)tR9;
- v) —(CH2)rNR8C(O)NH(CH2)tR9;
- and
- vi) —(CH2)rNR8C(NR8)NR8(CH2)tR9;
- R8 is hydrogen or C1-C3 linear alkyl;
- the index r is an integer from 0 to 4 and the index t is an integer form 0 to 4;
- R9 is phenyl or naphthyl;
- L3 comprises one or more units chosen from —CH2—, —CH═CH—, —C≡C—, —CH2CH2O—, —CH2CH2CH2O—, —CH2CH(CH3)O—, and —CH(CH3)CH2O—;
- L is a linking unit that comprises a fragmentable bond such that under the conditions of MALDI-MS or other mass spectrum conditions releases a stable cation having the formula:
An imaging agent having the formula:
An imaging agent having the formula:
- wherein AA is a naturally occurring or synthetic amino acid, xx is and integer from 1 to 7;
- Z has the formula:
- R1 an R2 are substituted or unsubstituted aryl groups chosen from phenyl, naphthyl, anthracenyl, phenanthrenyl, or tetracenyl;
- R3 is a substituted or unsubstituted aryl group chosen from phenyl, naphthyl, anthracenyl, phenanthrenyl, or tetracenyl, and wherein R3 further comprises an anchoring group having the formula:
- wherein Q is a unit having the formula:
- i) —(CH2)rC(O)O(CH2)tR9;
- ii) —(CH2)rOC(O)(CH2)tR9;
- iii) —(CH2)rC(O)NR8(CH2)tR9;
- iv) —(CH2)rNR8C(O)(CH2)tR9;
- v) —(CH2)rNR8C(O)NH(CH2)tR9;
- and
- vi) —(CH2)rNR8C(NR8)NR8(CH2)tR9;
- R8 is hydrogen or C1-C3 linear alkyl;
- the index r is an integer from 0 to 4 and the index t is an integer form 0 to 4;
- R9 is phenyl or naphthyl;
- L3 comprises one or more units chosen from —CH2, —CH═CH—, —C≡C—, —CH2CH2O—, —CH2CH2CH2O—, —CH2CH(CH3)O—, and —CH(CH3)CH2O—;
- L is a linking unit that comprises a fragmentable bond such that under the conditions of MALDI-MS or other mass spectrum conditions releases a stable cation having the formula:
The imaging agent 2-((2S,5S,8S,11S)-5-Benzyl-8-(1-(3-(5-(benzylamino)-5-oxopent-1-yn-1-yl)-4-methoxyphenyl)-1,1-bis(4-mentoxyphenyl)-5,14,23-trioxo-9,12,18,21-tetraoxa-2-thia-6,15,24-triazaoctancosan-28-yl)-11-(3-guanidinopropyl)-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentaazacyclopentadecan-2-yl)acetic acid having the formula:
An imaging agent having the formula:
- R1 an R2 are substituted or unsubstituted aryl groups chosen from phenyl, naphthyl, anthracenyl, phenanthrenyl, or tetracenyl;
- R3 is a substituted or unsubstituted aryl group chosen from phenyl, naphthyl, anthracenyl, phenanthrenyl, or tetracenyl, and wherein R3 further comprises an anchoring group having the formula:
- wherein Q is a unit having the formula:
- i) —(CH2)rC(O)O(CH2)tR9;
- ii) —(CH2)rOC(O)(CH2)tR9;
- iii) —(CH2)rC(O)NR8(CH2)tR9;
- iv) —(CH2)rNR8C(O)(CH2)tR9;
- v) —(CH2)rNR8C(O)NH(CH2)tR9;
- and
- vi) —(CH2)rNR8C(NR8)NR8(CH2)tR9;
- R8 is hydrogen or C1-C3 linear alkyl;
- the index r is an integer from 0 to 4 and the index t is an integer form 0 to 4;
- R9 is phenyl or naphthyl;
- L3 comprises one or more units chosen from —CH2—, —CH═CH—, —C≡C—, —CH2CH2O—, —CH2CH2CH2O—, —CH2CH(CH3)O—, and —CH(CH3)CH2O—;
- L is a linking unit that comprises a fragmentable bond such that under the conditions of MALDI-MS or other mass spectrum conditions releases a stable cation having the formula:
The imaging agent 18-(4-(((2-Amino-4-hydroxypteridin-6-yl)methyl)amino)benz-amido)-1-(1-(1-(3-(5-(benzylamino)-5-oxopent-1-yn-1-yl)-4-methoxyphenyl)-1,1-bis(4-methoxyphenyl)-5-oxo-10,13,16-trioxa-2-thia-6-azanonadecan-19-yl)-4-fluoro-4,5,6,7,8,9-hexahydro-1H-cycloocta[d][1,2,3]triazol-4-yl)-1,15-dioxo-5,8,11-trioxa-2,14-diazanonadecan-19-oic acid having the formula:
Dependencies are inferred from the claim text.