<html xmlns:v="urn:schemas-microsoft-com:vml" xmlns:o="urn:schemas-microsoft-com:office:office" xmlns:w="urn:schemas-microsoft-com:office:word" xmlns:x="urn:schemas-microsoft-com:office:excel" xmlns:m="http://schemas.microsoft.com/office/2004/12/omml" xmlns="http://www.w3.org/TR/REC-html40">
<head>
<meta http-equiv="Content-Type" content="text/html; charset=iso-8859-2">
<meta name="Generator" content="Microsoft Word 14 (filtered medium)">
<style><!--
/* Font Definitions */
@font-face
{font-family:"Cambria Math";
panose-1:2 4 5 3 5 4 6 3 2 4;}
@font-face
{font-family:Calibri;
panose-1:2 15 5 2 2 2 4 3 2 4;}
@font-face
{font-family:Tahoma;
panose-1:2 11 6 4 3 5 4 4 2 4;}
@font-face
{font-family:Verdana;
panose-1:2 11 6 4 3 5 4 4 2 4;}
/* Style Definitions */
p.MsoNormal, li.MsoNormal, div.MsoNormal
{margin:0cm;
margin-bottom:.0001pt;
font-size:10.0pt;
font-family:"Times New Roman","serif";
mso-fareast-language:FR;}
h6
{mso-style-priority:9;
mso-style-link:"Heading 6 Char";
margin-top:0cm;
margin-right:-14.2pt;
margin-bottom:0cm;
margin-left:-7.1pt;
margin-bottom:.0001pt;
text-align:center;
page-break-after:avoid;
font-size:16.0pt;
font-family:"Times New Roman","serif";
mso-fareast-language:FR;
font-weight:normal;}
p.MsoFooter, li.MsoFooter, div.MsoFooter
{mso-style-priority:99;
mso-style-link:"Footer Char";
margin:0cm;
margin-bottom:.0001pt;
font-size:10.0pt;
font-family:"Times New Roman","serif";
mso-fareast-language:FR;}
p.MsoTitle, li.MsoTitle, div.MsoTitle
{mso-style-priority:10;
mso-style-link:"Title Char";
margin-top:0cm;
margin-right:-14.2pt;
margin-bottom:0cm;
margin-left:-7.1pt;
margin-bottom:.0001pt;
text-align:center;
font-size:16.0pt;
font-family:"Times New Roman","serif";
mso-fareast-language:FR;
font-weight:bold;}
a:link, span.MsoHyperlink
{mso-style-priority:99;
color:blue;
text-decoration:underline;}
a:visited, span.MsoHyperlinkFollowed
{mso-style-priority:99;
color:purple;
text-decoration:underline;}
p.MsoAcetate, li.MsoAcetate, div.MsoAcetate
{mso-style-priority:99;
mso-style-link:"Balloon Text Char";
margin:0cm;
margin-bottom:.0001pt;
font-size:8.0pt;
font-family:"Tahoma","sans-serif";
mso-fareast-language:EN-US;}
span.Heading6Char
{mso-style-name:"Heading 6 Char";
mso-style-priority:9;
mso-style-link:"Heading 6";
font-family:"Times New Roman","serif";
mso-fareast-language:FR;}
span.FooterChar
{mso-style-name:"Footer Char";
mso-style-priority:99;
mso-style-link:Footer;
font-family:"Times New Roman","serif";
mso-fareast-language:FR;}
span.TitleChar
{mso-style-name:"Title Char";
mso-style-priority:10;
mso-style-link:Title;
font-family:"Times New Roman","serif";
mso-fareast-language:FR;
font-weight:bold;}
span.BalloonTextChar
{mso-style-name:"Balloon Text Char";
mso-style-priority:99;
mso-style-link:"Balloon Text";
font-family:"Tahoma","sans-serif";}
p.TAMainText, li.TAMainText, div.TAMainText
{mso-style-name:TA_Main_Text;
mso-style-priority:99;
margin:0cm;
margin-bottom:.0001pt;
text-indent:10.1pt;
line-height:200%;
font-size:12.0pt;
font-family:"Times New Roman","serif";
mso-fareast-language:EN-US;}
span.EmailStyle25
{mso-style-type:personal;
font-family:"Calibri","sans-serif";
color:windowtext;}
span.EmailStyle26
{mso-style-type:personal-reply;
font-family:"Calibri","sans-serif";
color:#1F497D;}
.MsoChpDefault
{mso-style-type:export-only;
font-size:10.0pt;}
@page WordSection1
{size:612.0pt 792.0pt;
margin:70.85pt 70.85pt 70.85pt 70.85pt;}
div.WordSection1
{page:WordSection1;}
--></style><!--[if gte mso 9]><xml>
<o:shapedefaults v:ext="edit" spidmax="1026" />
</xml><![endif]--><!--[if gte mso 9]><xml>
<o:shapelayout v:ext="edit">
<o:idmap v:ext="edit" data="1" />
</o:shapelayout></xml><![endif]-->
</head>
<body lang="SL" link="blue" vlink="purple">
<div class="WordSection1">
<p class="MsoTitle" style="margin:0cm;margin-bottom:.0001pt"><span style="font-size:18.0pt;font-family:"Verdana","sans-serif";color:black;font-weight:normal">VABILO NA INŠTITUTSKO PREDAVANJE / INVITATION TO THE INSTITUTE LECTURE<o:p></o:p></span></p>
<p class="MsoNormal" align="center" style="text-align:center"><b><span style="font-size:12.0pt;font-family:"Verdana","sans-serif""><o:p> </o:p></span></b></p>
<p class="MsoNormal" align="center" style="text-align:center;text-autospace:none">
<b><span style="font-size:20.0pt;font-family:"Verdana","sans-serif"">Prof. dr. Rona R. Ramsay<o:p></o:p></span></b></p>
<p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-GB" style="font-size:12.0pt;mso-fareast-language:EN-US">University of St Andrews, UK<o:p></o:p></span></p>
<p class="MsoNormal" align="center" style="text-align:center;line-height:150%"><span lang="FR" style="font-size:8.0pt;line-height:150%;font-family:"Verdana","sans-serif";mso-fareast-language:SL"><o:p> </o:p></span></p>
<p class="MsoNormal" align="center" style="text-align:center;line-height:150%"><b><span style="font-size:16.0pt;line-height:150%;font-family:"Verdana","sans-serif"">četrtek / Thursday, 5. 12. 2013, ob / at 13:00<o:p></o:p></span></b></p>
<h6 style="margin:0cm;margin-bottom:.0001pt"><span lang="EN-GB" style="font-size:14.0pt;mso-fareast-language:EN-US">Velika predavalnica Kemijskega inštituta / Lecture Hall at the
<o:p></o:p></span></h6>
<h6 style="margin:0cm;margin-bottom:.0001pt"><span lang="EN-GB" style="font-size:14.0pt;mso-fareast-language:EN-US">National Institute of Chemistry; Hajdrihova 19, Ljubljana
<o:p></o:p></span></h6>
<p class="MsoTitle" style="margin:0cm;margin-bottom:.0001pt"><span lang="EN-GB" style="font-size:14.0pt;mso-fareast-language:EN-US;font-weight:normal"><o:p> </o:p></span></p>
<p class="TAMainText" align="center" style="text-align:center;line-height:150%"><b><span lang="EN-GB" style="font-size:16.0pt;line-height:150%;font-family:"Verdana","sans-serif";color:#993366;mso-fareast-language:FR">Monoamine oxidase kinetics and drug design<o:p></o:p></span></b></p>
<p class="TAMainText" style="text-align:justify;line-height:normal"><span lang="EN-GB">Monoamine oxidase (MAO) is a target in the design of drugs for the treatment of depression, attention deficit disorders, Parkinson's Disease and Alzheimer's disease in order
to elevate the levels of depleted neurotransmitters. Increases in MAO A activity in heart and MAO B activity in brain with age have been linked with increased oxidative damage, providing another rationale for inhibiting these enzymes. MAO A and MAO B share
70% sequence identity and the same FAD cofactor covalently attached at a conserved cysteine residue. Their deep active site cavities are different in volume and shape conferring very different substrate and inhibitor specificities. The majority of MAOI drugs
in current use are mechanism-based irreversible inhibitors such as L-deprenyl (selegiline) which is selective for MAO B. Restoration of the activity is slow because human MAO turnover in brain has a half-life of 30 days. The irreversible inhibition of MAO
A in the gut results in tyramine in the blood and cardiovascular side-effects, so there are many series of new reversible inhibitors being published. In all this research, a key technique is eaperimental kinetic analysis. This lecture will cover kinetic experiments
from the last 20 years that have lead to our current understanding of the functional aspects including mechanism and inhibition of this important drug target.<o:p></o:p></span></p>
<p class="TAMainText" style="text-align:justify;line-height:normal"><span lang="EN-GB"><o:p> </o:p></span></p>
<p class="TAMainText" style="text-align:justify;text-indent:0cm;line-height:normal">
<b><span lang="EN-GB" style="font-size:8.0pt">Relevant articles</span></b><span lang="EN-GB" style="font-size:8.0pt">:<o:p></o:p></span></p>
<p class="TAMainText" style="text-align:justify;text-indent:0cm;line-height:normal">
<span lang="EN-GB" style="font-size:8.0pt">Ramsay RR. (2012) Monoamine Oxidases: The Biochemistry of the Proteins As Targets in Medicinal Chemistry and Drug Discovery.
<i>Current Topics in Medicinal Chemistry</i> 12:</span><span lang="EN-US" style="font-size:8.0pt"> 2189-2209.</span><span lang="EN-GB" style="font-size:8.0pt"><o:p></o:p></span></p>
<p class="TAMainText" style="text-align:justify;text-indent:0cm;line-height:normal">
<span lang="EN-US" style="font-size:8.0pt">Juárez-Jiménez J, Mendes E, Galdeano C, Martins C, Silva DB, Marco-Contelles J, et al. (2013) Exploring the structural basis of the selective inhibition of monoamine oxidase A by dicarbonitrile aminoheterocycles: Role
of Asn181 and Ile335 validated by spectroscopic and computational studies. <i>Biochim Biophys Acta (Proteins and Proteomics);
<b>in press</b></i>: <o:p></o:p></span></p>
<p class="TAMainText" style="text-indent:0cm;line-height:normal"><span lang="EN-US" style="font-size:8.0pt">McDonald GR, Olivieri A, Ramsay RR, Holt A (2010) On the formation and nature of the imidazoline I(2) binding site on human monoamine oxidase-B.
<i>Pharmacol Res; </i><b>62</b>: 475-88.<o:p></o:p></span></p>
<p class="TAMainText" style="text-indent:0cm;line-height:normal"><span lang="EN-US" style="font-size:8.0pt">Tan, A.K. and R.R. Ramsay. Substrate-specific Enhancement of the Oxidative Half-reaction of Monoamines Oxidase,
<i>Biochemistry </i> <b>32,</b> 2137-2143. (1993). <o:p></o:p></span></p>
<p class="MsoNormal"><span lang="FR" style="font-size:8.0pt">Vianello, R.; Repic, M.; Mavri, J. (2012) How are Biogenic Amines Metabolized by Monoamine Oxidases?
<i>EUROPEAN JOURNAL OF ORGANIC CHEMISTRY </i>36: 7057-7065 DOI: 10.1002/ejoc.201201122<o:p></o:p></span></p>
<p class="MsoNormal"><span lang="FR" style="font-size:8.0pt">Edmondson, Dale E.; Binda, Claudia; Wang, Jin; et al. (2009) Molecular and Mechanistic Properties of the Membrane-Bound Mitochondrial Monoamine Oxidases.
<i>BIOCHEMISTRY</i> 48: 4220-4230 DOI: 10.1021/bi900413g <o:p></o:p></span></p>
<p class="MsoNormal" style="text-indent:18.0pt"><span lang="EN-GB" style="font-size:11.0pt;font-family:"Arial","sans-serif""><o:p> </o:p></span></p>
<p class="MsoNormal" style="text-align:justify"><span lang="EN-GB" style="font-size:8.0pt;font-family:"Arial","sans-serif";color:#333333"><o:p> </o:p></span></p>
<p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-US" style="font-size:12.0pt;font-family:"Arial","sans-serif";mso-fareast-language:SL">Vljudno vabljeni! / Kindly invited!<o:p></o:p></span></p>
<p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-US" style="font-size:12.0pt;font-family:"Arial","sans-serif";mso-fareast-language:SL"><o:p> </o:p></span></p>
<p class="MsoFooter" align="center" style="text-align:center"><span lang="FR" style="font-size:11.0pt;font-family:"Verdana","sans-serif"">Info: Janez Mavri;
<a href="mailto:janez.mavri@ki.si">janez.mavri@ki.si</a> <o:p></o:p></span></p>
<p class="MsoFooter" align="center" style="text-align:center"><span lang="FR" style="font-size:11.0pt;font-family:"Verdana","sans-serif""><o:p> </o:p></span></p>
<p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-US" style="font-size:12.0pt;font-family:"Arial","sans-serif";mso-fareast-language:SL"><o:p> </o:p></span></p>
<p class="MsoNormal"><span lang="EN-US" style="font-family:"Verdana","sans-serif""><o:p> </o:p></span></p>
<p class="MsoNormal"><span lang="FR"><o:p> </o:p></span></p>
</div>
</body>
</html>