From a cDNA library of mouse skeletal muscle, we have isolated mouse Sim1 (mSim1) cDNA encoding a polypeptide of 765 amino acids with striking amino acid identity in basic helix-loop-helix (89% identity) and PAS (89% identity) domains to previously identified mSim2, although the carboxy-terminal third of the molecule did not show any similarity to mSim2 or Drosophila Sim (dSim). Whole-mount in situ hybridization showed restricted and characteristic expression patterns of the two mSim mRNAs in various tissues and organs during embryogenesis, such as those for the somite, the nephrogenic cord, and the mesencephalon (for mSim1) and those for the diencephalon, branchial arches, and limbs (for mSim2). From sequence similarity and chromosomal localization, it is concluded that mSim2 is an ortholog of hSIM2, which is proposed to be a candidate gene responsible for Down's syndrome. The sites of mSim2 expression showed an overlap with the affected regions of the syndrome, further strengthening involvement of mSim2 in Down's syndrome.

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A major problem in polypeptide synthesis is the formation of products with a wide range of molecular weights. As a step toward the total synthesis of natural protein, an attempt was made to synthesize a sequential polypeptide with a defined molecular weight. Thus, poly-(L-prolyl-L-prolylglycyl) with ten or twenty repeating units was synthesized by the step-by-step addition of AOC-L-prolyl-L-prolylglycine (I)1) using the solid-phase procedure.2) The synthesis was started from glycine-anchored polystyrene (100-200 mesh, copolymerized with 2% divinylbenzene; 14g, 0.1mmol/g), to which AOC-L-prolyl-L-proline (1.4g)1) was coupled in methylene chloride with dicyclohexylcarbodiimide. The AOCgroup was then removed with 2N hydrogen chloride in acetic acid, and the tripeptide-cycle was extended with I (1.7g per cycle) and dicyclohexylcarbodiimide (0.9g per cycle); each coupling reaction was carried out in methylene chloride for 3hr at room temperature. After nine reaction cycles, when ten repeating units were expected to have been formed, a part of the resin was dried (wt 7g) and placed in an HFreaction cylinder;3) anisole (7ml) was added, and then anhydrous hydrogen fluoride (HF, was introduced over the resin by means of the HFexcess HF was removed, and the peptide liberated was extracted with water. The water extract was treated with IR-45 (OH-form), and then dialyzed against distilled water for 3 days. The final solution was lyophilized (II, wt 0.

Background: The Arnt3 (also termed as BMAL1 or MOP3)/Clock heterodimer is a positive regulator of circadian rhythm and activates the transcription of target genes such as per1 and vasopressin.

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