849191-03-3Relevant academic research and scientific papers
Quantitative insight into the design of compounds recognized by the L-type amino acid transporter 1 (LAT1)
Ylikangas, Henna,Malmioja, Kalle,Peura, Lauri,Gynther, Mikko,Nwachukwu, Emmanuel O.,Lepp?nen, Jukka,Laine, Krista,Rautio, Jarkko,Lahtela-Kakkonen, Maija,Huttunen, Kristiina M.,Poso, Antti
, p. 2699 - 2707 (2015/02/02)
L-Type amino acid transporter 1 (LAT1) is a transmembrane protein expressed abundantly at the blood-brain barrier (BBB), where it ensures the transport of hydrophobic acids from the blood to the brain. Due to its unique substrate specificity and high expression at the BBB, LAT1 is an intriguing target for carrier- mediated transport of drugs into the brain. In this study, a comparative molecular field analysis (CoMFA) model with considerable statistical quality (Q2=0.53, R2=0.75, Q2 SE=0.77, R2 SE=0.57) and good external predictivity (CCC=0.91) was generated. The model was used to guide the synthesis of eight new prodrugs whose affinity for LAT1 was tested by using an in situ rat brain perfusion technique. This resulted in the creation of a novel LAT1 prodrug with l-tryptophan as the promoiety; it also provided a better understanding of the molecular features of LAT1-targeted high-affinity prodrugs, as well as their promoiety and parent drug. The results obtained will be beneficial in the rational design of novel LAT1-binding prodrugs and other compounds that bind to LAT1.
Studies on the synthesis and biosynthesis of the fungal alkaloid necatorone
Carstens, J?rn,Heinrich, Markus R.,Steglich, Wolfgang
supporting information, p. 5445 - 5447 (2013/09/23)
An alternative pathway for the biosynthesis of the fungal alkaloid necatorone has been studied using fluorine-labeled 3-(2-carboxyphenylamino)-l- tyrosine. Although no incorporation of this compound could be detected in feeding experiments with young specimens of Lactarius necator, an analogous 3-aminotyrosine derivative could be converted synthetically into the oxopyridoacridine core structure of necatorone. In experiments aimed at the synthesis of aaptamine-type alkaloids, an unprecedented cyclization of a 3-aminotyrosine-methyl propiolate adduct to a methyl isoquinoline-3-carboxylate was observed. A mechanism is proposed, in which C3 of the propiolate delivers C1 of the isoquinoline nucleus.
