TY - JOUR
T1 - S-functionalized cysteine
T2 - Powerful ligands for the labelling of bioactive molecules with triaquatricarbonyltechnetium-99m(1 +) ([99mTc(OH 2)3(CO)3]+)
AU - Van Staveren, Dave R.
AU - Benny, Paul D.
AU - Waibel, Robert
AU - Kurz, Philipp
AU - Pak, Jae Kyoung
AU - Alberto, Roger
PY - 2005
Y1 - 2005
N2 - S-Alkylated cysteines are used as efficient tridentate N,O,S-donor-atom ligands for the fac-[M(CO)3]+ moiety (M = 99mTc or Re). Reaction of (Et4N)2[ReBr3(CO) 3] (3) with the model S-benzyl-L-cysteine (2) leads to the formation of [Re(2′)(CO)3] (4) as the exclusive product (2′ = C-terminal anion of 2). The tridentate nature of the alkylated cysteine in 4 was established by X-ray crystallography. Compound 2 reacts with [ 99mTc(OH2)3(CO)3]+ under mild conditions (10-4 M, 50°, 30 min) to afford [ 99mTc(2′)(CO)3] (5) and represents, therefore, an efficient chelator for the labelling of biomolecules. L-Cysteine, S-alkylated with a 3-aminopropyl group (→ 7), was conjugated via a peptide coupling sequence with Coα-[α-(5,6-dimethyl-1H-benzimidazolyl)]-Coβ- cyanocobamic b-acid (6), the b-acid of cyanocob(III)alamin (vitamin B 12) (Scheme 3). More convenient was a one-pot procedure with a derivative of vitamin B12 comprising a free amine group at the b-position. This amine 15 was treated with NHS (N-hydroxysuccinimide)-activated 1-iodoacetic acid 14 to introduce an I-substituent in vitamin B12. Subsequent addition of unprotected L-cysteine resulted in nucleophilic displacement of the I-atom by the S-substituent, affording the vitamin B 12 alkylated cysteine fragment 17 (Scheme 4). The procedure was quantitative and did not require purification of intermediates. Both cobalamin-cysteine conjugates could be efficiently labelled with [ 99mTc(OH2)3(CO)3]+ (1) under conditions identical to those of the model complex 5. Biodistribution studies of the cobalamin conjugates in mice bearing B10-F16 melanoma tumors showed a tumor uptake of 8.1 ± 0.6% and 4.4 ± 0.5% injected dose per gram of tumor tissue after 4 h and 24 h, respectively (Table 1).
AB - S-Alkylated cysteines are used as efficient tridentate N,O,S-donor-atom ligands for the fac-[M(CO)3]+ moiety (M = 99mTc or Re). Reaction of (Et4N)2[ReBr3(CO) 3] (3) with the model S-benzyl-L-cysteine (2) leads to the formation of [Re(2′)(CO)3] (4) as the exclusive product (2′ = C-terminal anion of 2). The tridentate nature of the alkylated cysteine in 4 was established by X-ray crystallography. Compound 2 reacts with [ 99mTc(OH2)3(CO)3]+ under mild conditions (10-4 M, 50°, 30 min) to afford [ 99mTc(2′)(CO)3] (5) and represents, therefore, an efficient chelator for the labelling of biomolecules. L-Cysteine, S-alkylated with a 3-aminopropyl group (→ 7), was conjugated via a peptide coupling sequence with Coα-[α-(5,6-dimethyl-1H-benzimidazolyl)]-Coβ- cyanocobamic b-acid (6), the b-acid of cyanocob(III)alamin (vitamin B 12) (Scheme 3). More convenient was a one-pot procedure with a derivative of vitamin B12 comprising a free amine group at the b-position. This amine 15 was treated with NHS (N-hydroxysuccinimide)-activated 1-iodoacetic acid 14 to introduce an I-substituent in vitamin B12. Subsequent addition of unprotected L-cysteine resulted in nucleophilic displacement of the I-atom by the S-substituent, affording the vitamin B 12 alkylated cysteine fragment 17 (Scheme 4). The procedure was quantitative and did not require purification of intermediates. Both cobalamin-cysteine conjugates could be efficiently labelled with [ 99mTc(OH2)3(CO)3]+ (1) under conditions identical to those of the model complex 5. Biodistribution studies of the cobalamin conjugates in mice bearing B10-F16 melanoma tumors showed a tumor uptake of 8.1 ± 0.6% and 4.4 ± 0.5% injected dose per gram of tumor tissue after 4 h and 24 h, respectively (Table 1).
UR - http://www.scopus.com/inward/record.url?scp=16644401051&partnerID=8YFLogxK
U2 - 10.1002/hlca.200590029
DO - 10.1002/hlca.200590029
M3 - Article
AN - SCOPUS:16644401051
SN - 0018-019X
VL - 88
SP - 447
EP - 460
JO - Helvetica Chimica Acta
JF - Helvetica Chimica Acta
IS - 3
ER -