<html><head></head><body style="word-wrap: break-word; -webkit-nbsp-mode: space; -webkit-line-break: after-white-space; "><!--StartFragment--><div style="margin-top: 0in; margin-right: -0.5in; margin-left: 2in; margin-bottom: 0.0001pt; text-align: left; text-indent: 0.5in; "><span style="font-family:"Times New Roman""><b><font class="Apple-style-span" size="4"><span class="Apple-style-span" style="font-size: 14px;"><span class="Apple-tab-span" style="white-space:pre"> </span>Seminar on<o:p></o:p></span></font></b></span></div><p class="MsoTitle" style="margin-right:-.5in"><span style="font-family: 'Times New Roman'; "><b><font class="Apple-style-span" size="4"><span class="Apple-style-span" style="font-size: 14px;"> <o:p></o:p></span></font></b></span></p><p class="MsoNormal" align="center" style="text-align:center"><span style="letter-spacing: 1.5pt; "><b><font class="Apple-style-span" size="4"><span class="Apple-style-span" style="font-size: 14px;">Modern Optics and Spectroscopy<o:p></o:p></span></font></b></span></p>
<div class="MsoNormal"><span style="font-family: Arial; letter-spacing: 1pt; "><b><font class="Apple-style-span" size="4"><span class="Apple-style-span" style="font-size: 14px;"> <o:p></o:p></span></font></b></span></div><p class="MsoBodyText" style="margin-right:-29.9pt"><span style="color: black; font-style: normal; "><font class="Apple-style-span" size="4"><span class="Apple-style-span" style="font-size: 14px;"><span class="Apple-tab-span" style="white-space:pre"> </span>The pH Low Insertion Peptides (pHILIPs): Mechanism of Insertion and Medical
Applications<o:p></o:p></span></font></span></p><p class="MsoNormal" align="center" style="text-align:center"><span style="letter-spacing: 1pt; "><b><font class="Apple-style-span" size="4"><span class="Apple-style-span" style="font-size: 14px;"> <o:p></o:p></span></font></b></span></p><p class="MsoNormal" align="center" style="text-align:center"><b><font class="Apple-style-span" size="4"><span class="Apple-style-span" style="font-size: 14px;">Oleg A. Andreev</span></font></b><span style="letter-spacing: 1pt; "><font class="Apple-style-span" size="4"><span class="Apple-style-span" style="font-size: 14px;">, <o:p></o:p></span></font></span></p><p class="MsoNormal" align="center" style="text-align:center"><span style="letter-spacing: 1pt; "><font class="Apple-style-span" size="4"><span class="Apple-style-span" style="font-size: 14px;">University of Rhode Island<o:p></o:p></span></font></span></p><p class="MsoNormal" align="center" style="text-align:center"><span style="letter-spacing: 1pt; "><font class="Apple-style-span" size="4"><span class="Apple-style-span" style="font-size: 14px;"> <o:p></o:p></span></font></span></p><p class="MsoNormal" align="center" style="text-align:center"><span style="letter-spacing: 1pt; "><font class="Apple-style-span" size="4"><span class="Apple-style-span" style="font-size: 14px;">Tuesday, May 3, 2011</span></font></span><span style="letter-spacing: 1pt; "><font class="Apple-style-span" size="4"><span class="Apple-style-span" style="font-size: 14px;"><o:p></o:p></span></font></span></p><p class="MsoNormal" align="center" style="text-align:center"><span style="letter-spacing: 1pt; "><font class="Apple-style-span" size="4"><span class="Apple-style-span" style="font-size: 14px;"> <o:p></o:p></span></font></span></p><p class="MsoNormal" align="center" style="text-align:center"><span style="letter-spacing: 1pt; "><font class="Apple-style-span" size="4"><span class="Apple-style-span" style="font-size: 14px;">12:00 – 1:00 p.m.<o:p></o:p></span></font></span></p><p class="MsoNormal" align="center" style="text-align:center"><font class="Apple-style-span" face="Arial" size="4"><span class="Apple-style-span" style="font-size: 14px; letter-spacing: 1px;"><br></span></font></p>
<div class="MsoNormal"><font class="Apple-style-span" size="4"><span class="Apple-style-span" style="font-size: 14px;">The pH Low Insertion Peptides
(pHLIPs) are membrane peptides that insert in membrane at low pH (<7.0) and
do not at physiological (7.4) or <a name="_GoBack"></a>higher pH. We
investigated mechanism of insertion of pHLIP and found that protonation of Asp
residues increases the hydrophobicity of peptide and triggers insertion and
formation of transmembrane helix.
Insertion of pHLIP is accompanied with significant changes in tryptophan
fluorescence and CD spectra. We found that after drop of pH a helix is formed first
and then transmembrane configuration is adopted with the C-terminus is inside
of liposome or cell and the N-terminus staying outside a membrane. Since the
affinity of pHLIP to membrane is higher at low pH we came to an idea to use
pHLIP to target acidic diseased tissue in vivo. It is well known that solid
tumors develop an acidic extracellular environment due to shift of cancer cells
to glycolytic pathway of energy production (Warburg effect). Indeed, we proved
that pHLIP labeled with various imaging agents can find and stained primary
tumors and metastatic lesions of even very small sizes. pHLIP can be used as a
tumor targeting agent and it can deliver small molecules, nanoparticles and
liposomes to tumors in vivo. Since the C-terminus of pHLIP inserts across
membrane it can translocate cell impermeable molecules into cytoplasm acting as a
single-molecular transporter or nanosyringe. We demonstrated that pHLIP can
translocate several biologically functional molecules across a membrane and
release them inside cells. The
ability of pHLIP to find cancer cells and translocate molecules across membrane
opens new opportunity for targeted cancer therapy. pHLIP represents a novel
class of theranostic agents for imaging
and treatment of tumors. <o:p></o:p></span></font></div>
<div class="MsoNormal"><font class="Apple-style-span" size="4"><span class="Apple-style-span" style="font-size: 14px;"> <o:p></o:p></span></font></div>
<div class="MsoNormal"><font class="Apple-style-span" size="4"><span class="Apple-style-span" style="font-size: 14px;"> <o:p></o:p></span></font></div><p class="MsoNormal" align="center" style="text-align:center"><font class="Apple-style-span" size="4"><span class="Apple-style-span" style="font-size: 14px;">Grier Room, MIT Bldg 34-401<o:p></o:p></span></font></p><p class="MsoNormal" align="center" style="text-align:center"><font class="Apple-style-span" size="4"><span class="Apple-style-span" style="font-size: 14px;">Refreshments served after the lecture</span></font><o:p></o:p></p>
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