We have developed an alternate and effective pathway for completely protected peptide nucleic acid (PNA) monomer synthesis. The process involves alkylation of nosyl protected amino acids with N-Boc protected bromoethyl amine followed by deprotection of the nosyl group and condensation of thymine-1-acetic acid which was chosen as a nucleobase. The key intermediates, chiral/achiral PNA backbone, were obtained with an average overall yield of 50-60%. The glycine, valine, alanine and serine derived PNA monomers were prepared in four steps, starting from readily available materials and this result suggests that our approach is executable in all amino acids.

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Fetal alcohol spectrum disorder (FASD) results from prenatal ethanol exposure. The zebrafish (Danio rerio) is an outstanding in vivo FASD model. Early development produced the three germ layers and embryonic axes patterning. A critical pluripotency transcriptional gene circuit of sox2, pou5f1 (oct4; recently renamed pou5f3), and nanog maintain potency and self-renewal. Ethanol affects sox2 expression, which functions with pou5f1 to control target gene transcription. Various genes, like elf3, may interact and regulate sox2, and elf3 knockdown affects early development. Downstream of the pluripotency transcriptional circuit, developmental signaling activities regulate morphogenetic cell movements and lineage specification. These activities are also affected by ethanol exposure. Hedgehog signaling is a critical developmental signaling pathway that controls numerous developmental events, including neural axis specification. Sonic hedgehog activities are affected by embryonic ethanol exposure. Activation of sonic hedgehog expression is controlled by TGF-ß family members, Nodal and Bmp, during dorsoventral (DV) embryonic axis establishment. Ethanol may perturb TGF-ß family receptors and signaling activities, including the sonic hedgehog pathway. Significantly, experiments show that activation of sonic hedgehog signaling rescues some embryonic ethanol exposure effects. More research is needed to understand how ethanol affects early developmental signaling and morphogenesis.

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