Synthesis and Characterization of YYGSR-NH2 as a Chemical Starting Poin for Thyroid Theranostic Radiopharmaceutical Development

Thyroid cancer is an endocrine malignancy that still requires the development of more targeted diagnostic and therapeutic approaches. Peptides are promising chemical platforms for radiopharmaceutical development because they can be synthesized in a controlled manner and chemically modified. This study aimed to synthesize and characterize YYGSR-NH₂ as a chemical starting point for thyroid theranostic radiopharmaceutical development. YYGSR-NH₂ was synthesized using Fmoc-solid phase peptide synthesis on Fmoc-Rink amide resin through sequential coupling of Arg, Ser, Gly, Tyr, and Tyr residues. Deprotection was performed using 20% piperidine in DMF, while coupling was carried out using HATU, HOAt, and DIPEA. The peptide was cleaved from the resin using TFA/TIS/H₂O, purified by semi-preparative RP-HPLC, and characterized using analytical RP-HPLC and time-of-flight mass spectrometry. The resin loading obtained was 0.546 mmol/g, with an average crude product mass of 0.4739 g. Semi-preparative HPLC showed several components with major peaks at retention times of approximately 12–14 min. Analytical HPLC showed two peaks at retention times of 1.315 and 26.412 min, with relative areas of 96.31% and 3.69%, respectively. Mass spectrometry showed a dominant ion at m/z 644.3157, which was consistent with the theoretical [M+H]⁺ ion of YYGSR-NH₂. Based on these results, YYGSR-NH₂ was successfully synthesized and its molecular identity was confirmed by mass spectrometry, supporting its use as a chemical starting point for further development of thyroid theranostic radiopharmaceuticals.