The protonation constants of tryptophan (K 1 and K 2) were determined in binary mixtures of water with methanol, ethanol, and 1-propanol containing (0, 10, 20, 30, 40, 50, 60, 70, and 80) % (v/v) using a potentiometric method at 25 °C and constant ionic strength (0.1 mol·dm−3 sodium perchlorate). The autoprotolysis constant values (K ap) of the media were also determined in the same binary mixtures. The protonation constants of tryptophan and the autoprotolysis constant of the medium in different binary mixtures were analyzed in terms of Kamlet, Abboud, and Taft (KAT) parameters. Single-parameter correlations of the constants versus α (hydrogen-bond donor acidity), β (hydrogen-bond acceptor basicity), and π* (dipolarity/polarizability) are poor in all solutions. Multiparameter correlations show better results, but dual-parameter correlations represent significant improvements with regard to the single- and multiparameter models. Linear correlation is observed when the experimental log K ap, log K 1, and log K 2 values are plotted versus the calculated ones, while the KAT parameters are considered. Finally, the results are discussed in terms of the effect of the solvent on the protonation and autoprotolysis constants.

No abstract

Prostate cancer is a serious threat to men's health, so it is necessary to develop the techniques for early detection of this malignancy. Radiolabeled peptides are the useful tools for diagnosis of prostate cancer. In this research, we designed a new HYNIC‐conjugated GnRH analogue and labeled it by 99mTc with tricine/EDDA as coligands. We used aminohexanoic acid (Ahx) as a hydrocarbon linker to generate 99mTc‐(tricine/EDDA)‐HYNIC‐Ahx‐[DLys6]GnRH. The radiopeptide exhibited high radiochemical purity and stability in solution and serum. Two human prostate cancer cell lines LN‐CaP and DU‐145 were used for cellular experiments. The binding specificity and affinity of radiopeptide for LN‐CaP were superior to DU‐145 cells. The Kd values for LN‐CaP and DU‐145 cells were 41.91 ± 7.03 nM and 55.96 ± 10.56 nM, respectively. High kidney uptake proved that the main excretion route of radiopeptide was through the urinary system. The tumor/muscle ratio of 99mTc‐HYNIC‐Ahx‐[DLys6]GnRH was 4.14 at 1 hr p.i. that decreased to 2.41 at 4 hr p.i. in LN‐CaP tumor‐xenografted nude mice. The blocking experiment revealed that the tumor uptake was receptor‐mediated. The lesion was visualized clearly using 99mTc‐[DLys6]GnRH at 1 hr p.i. Accordingly, this research highlights the capability of 99mTc‐(tricine/EDDA)‐HYNIC‐Ahx‐[DLys6]GnRH peptide as a promising agent for GnRHR‐expressing tumor imaging.

No abstract

The aim of this study was to prepare radiolabeled peptide‐based agents for imaging of colon cancer. According to the incorporation of HYNIC for radiolabeling with technetium‐99m, two analogs were designed and compared: an antitumor‐antibody‐derived peptide based on the EPPT sequence and a novel retro‐inverso peptidomimetic derivative D(TPPE) structurally modified by replacing the L‐amino acids with D‐amino acids and reversing the primary amino acid sequence of EPPT. The HYNIC‐conjugated peptides were labeled with 99mTc using tricine/EDDA coligand with more than 98% radiochemical yield and showed high metabolic stability. Kd values of 41.77 ± 7.34 nM and 37.33 ± 8.37 nM for 99mTc‐HYNIC‐EPPT and 99mTc‐HYNIC‐D(TPPE) confirmed high affinity of both peptides for cell surface antigen MUC1. These radiotracers demonstrated no significant differences in the cellular uptake and internalization value, but the biodistribution profile of 99mTc‐HYNIC‐D(TPPE) was more favorable than that of 99mTc‐HYNIC‐EPPT as a result of better tumor‐to‐non‐target ratios for the examined tissues and organs. HT29 tumors were visualized more clearly in scintigraphic images with 99mTc‐HYNIC‐D(TPPE) in comparison with 99mTc‐HYNIC‐EPPT. The results showed the retro‐inverso analog to be a more promising radiotracer as a probe for in vivo targeting of HT‐29 tumors than the parent peptide.