<?xml version="1.0" encoding="ISO-8859-1"?><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
<front>
<journal-meta>
<journal-id>2224-6185</journal-id>
<journal-title><![CDATA[Tecnología Química]]></journal-title>
<abbrev-journal-title><![CDATA[RTQ]]></abbrev-journal-title>
<issn>2224-6185</issn>
<publisher>
<publisher-name><![CDATA[Universidad de Oriente]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S2224-61852024000100005</article-id>
<title-group>
<article-title xml:lang="es"><![CDATA[Evaluación de un nuevo esquema de purificación de la muteína interleukina-2]]></article-title>
<article-title xml:lang="en"><![CDATA[Evaluation of a new non-alpha il-2 mutein purification scheme]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Llanes-Cuesta]]></surname>
<given-names><![CDATA[María Gabriela]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Montes de Oca-Garc´&#305;a]]></surname>
<given-names><![CDATA[Daidé]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Zumalacarregui-de Cárdenas]]></surname>
<given-names><![CDATA[Lourdes]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
</contrib-group>
<aff id="Af1">
<institution><![CDATA[,Universidad Tecnológica de La Habana José Antonio Echeverr´&#305;a, CUJAE Departamento de Ingeniería Química ]]></institution>
<addr-line><![CDATA[La Habana ]]></addr-line>
<country>Cuba</country>
</aff>
<aff id="Af2">
<institution><![CDATA[,Centro de Inmunología Molecular  ]]></institution>
<addr-line><![CDATA[La Habana ]]></addr-line>
<country>Cuba</country>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>04</month>
<year>2024</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>04</month>
<year>2024</year>
</pub-date>
<volume>44</volume>
<numero>1</numero>
<fpage>5</fpage>
<lpage>28</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://scielo.sld.cu/scielo.php?script=sci_arttext&amp;pid=S2224-61852024000100005&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://scielo.sld.cu/scielo.php?script=sci_abstract&amp;pid=S2224-61852024000100005&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://scielo.sld.cu/scielo.php?script=sci_pdf&amp;pid=S2224-61852024000100005&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="es"><p><![CDATA[RESUMEN La elución por Imidazol se utiliza en la etapa de captura del proceso de purificación de la muteína Interleukina-2 no alfa, específicamente en la cromatografía de afinidad de quelatos metálicos inmovilizados (IMAC). Para demostrar que es posible una nueva forma de elución en IMAC haciendo uso de soluciones menos costosas, se realizaron cambios en esta etapa: separar la cromatografía de exclusión molecular y la oxidación controlada (se realizan actualmente de forma conjunta), además de cambiar la solución de elución. Para lograr el objetivo, se realizó un diseño de experimentos factorial 22 evaluando el efecto del pH y la concentración molar en el recobrado, la pureza y el diámetro de partícula. Los mejores resultados se obtuvieron con la solución de acetato de sodio 20 mmol L-1 pH 4, siendo similares a los obtenidos hoy en la industria: 29 % de recobrado, 90 % de pureza y un diámetro de partícula de 18,40 nm. La primera contribución de este trabajo es demostrar la viabilidad de utilizar la nueva metodología de elución. Haciendo uso del software académico SuperPro Designer, se simuló, verificó y validó esta etapa. Con el propósito de demostrar la relación entre costos y beneficios, siendo la segunda contribución de este trabajo, se incrementó el volumen de gel de la matriz CH SFF. Este cambio resultó en un aumento de los costos en esta etapa. Sin embargo, la productividad obtenida creció en 109 mg h-1, siendo 2,78 veces mayor a la productividad actual, acrecentándose los ingresos en $ 879 325,00.]]></p></abstract>
<abstract abstract-type="short" xml:lang="en"><p><![CDATA[ABSTRACT The elution by imidazole is used in the purification process of non-alpha IL-2 mutein, specifically in the immobilized metal chelates affinity chromatography step (IMAC). In order to demonstrate that a new elution process is possible using cheaper solutions, changes were made in the former capture step. These changes consist on separate the size exclusion chromatography and the controlled oxidation stage which are currently performed together, as well as changing the elution solution. To achieve this, a 22 factorial design of experiments was performed to evaluate the effect of pH and molar concentration on recovery, purity, and particle diameter. The best results were obtained with the solution of sodium acetate 20 mmol L-1 pH 4 being similar to those obtained in the industry nowadays: 29 % recovery, 90 % of purity, and particle diameter 18,40 nm. The first contribution of this paper is to demonstrate the feasibility of using the new elution methodology. Moreover, by using the academic software SuperPro Designer, the actual capture step of the purification process (elution by Imidazole) was simulated, validated, and verified. To demonstrate the relationship between costs and benefits, the CH SFF matrix gel volume was incremented. This change increased costs at this stage. However, the productivity obtained grew to 109 mg h-1, 2.78 times greater than the current productivity. Therefore, the gross net increased by 879 325,00 $. This result constitutes the second contribution of this paper.]]></p></abstract>
<kwd-group>
<kwd lng="en"><![CDATA[mutein]]></kwd>
<kwd lng="en"><![CDATA[design of experiments]]></kwd>
<kwd lng="en"><![CDATA[productivity]]></kwd>
<kwd lng="en"><![CDATA[simulation]]></kwd>
<kwd lng="en"><![CDATA[SuperPro Designer]]></kwd>
<kwd lng="es"><![CDATA[muteína]]></kwd>
<kwd lng="es"><![CDATA[diseño de experimentos]]></kwd>
<kwd lng="es"><![CDATA[productividad]]></kwd>
<kwd lng="es"><![CDATA[simulación]]></kwd>
<kwd lng="es"><![CDATA[SuperPro Designer]]></kwd>
</kwd-group>
</article-meta>
</front><back>
<ref-list>
<ref id="B1">
<label>1</label><nlm-citation citation-type="book">
<source><![CDATA[]]></source>
<year>2020</year>
<publisher-name><![CDATA[National Cancer Institute]]></publisher-name>
</nlm-citation>
</ref>
<ref id="B2">
<label>2</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[KLATZMANN]]></surname>
<given-names><![CDATA[D.]]></given-names>
</name>
<name>
<surname><![CDATA[ABBAS]]></surname>
<given-names><![CDATA[A.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[The promise of low-dose Interleukin-2 therapy for autoimmune and inflammatory diseases]]></article-title>
<source><![CDATA[Nature Reviews Immunology]]></source>
<year>2015</year>
<volume>15</volume>
<page-range>283-94</page-range></nlm-citation>
</ref>
<ref id="B3">
<label>3</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[KHORYATI]]></surname>
<given-names><![CDATA[L.]]></given-names>
</name>
<name>
<surname><![CDATA[NGUYET PHAM]]></surname>
<given-names><![CDATA[M.]]></given-names>
</name>
<name>
<surname><![CDATA[SHERVE]]></surname>
<given-names><![CDATA[M.]]></given-names>
</name>
<name>
<surname><![CDATA[KUMARI]]></surname>
<given-names><![CDATA[S.]]></given-names>
</name>
<name>
<surname><![CDATA[COOK]]></surname>
<given-names><![CDATA[K.]]></given-names>
</name>
<name>
<surname><![CDATA[PEARSON]]></surname>
<given-names><![CDATA[J.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[An IL-2 mutein engineered to promote the expansion of regulatory T cells arrests ongoing autoimmunity in mice]]></article-title>
<source><![CDATA[Science Immunology]]></source>
<year>2020</year>
<volume>5</volume>
<numero>50</numero>
<issue>50</issue>
</nlm-citation>
</ref>
<ref id="B4">
<label>4</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[CARMENATE]]></surname>
<given-names><![CDATA[T.]]></given-names>
</name>
<name>
<surname><![CDATA[LEN]]></surname>
<given-names><![CDATA[K.]]></given-names>
</name>
<name>
<surname><![CDATA[ROJAS]]></surname>
<given-names><![CDATA[G.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Diseño, obtención y evaluación de una muteína derivada de la IL-2 humana para el uso en la terapia antitumoral]]></article-title>
<source><![CDATA[Anales de la Academia de Ciencias de Cuba]]></source>
<year>2016</year>
<volume>6</volume>
<numero>3</numero>
<issue>3</issue>
</nlm-citation>
</ref>
<ref id="B5">
<label>5</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[ARENA-RAMIREZ]]></surname>
<given-names><![CDATA[N.]]></given-names>
</name>
<name>
<surname><![CDATA[WOYTSCHAK]]></surname>
<given-names><![CDATA[J.]]></given-names>
</name>
<name>
<surname><![CDATA[BOYMAN]]></surname>
<given-names><![CDATA[O.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Interleukin-2: Biology, Design and Applications]]></article-title>
<source><![CDATA[Trends in Immunology]]></source>
<year>2015</year>
<volume>35</volume>
<numero>12</numero>
<issue>12</issue>
</nlm-citation>
</ref>
<ref id="B6">
<label>6</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[CROWLEY]]></surname>
<given-names><![CDATA[S.]]></given-names>
</name>
<name>
<surname><![CDATA[BRUCK]]></surname>
<given-names><![CDATA[P.]]></given-names>
</name>
<name>
<surname><![CDATA[BHUIYAN]]></surname>
<given-names><![CDATA[M.]]></given-names>
</name>
<name>
<surname><![CDATA[MITCHELL]]></surname>
<given-names><![CDATA[A.]]></given-names>
</name>
<name>
<surname><![CDATA[WALSH]]></surname>
<given-names><![CDATA[M.J.]]></given-names>
</name>
<name>
<surname><![CDATA[ZHANGXY]]></surname>
<given-names><![CDATA[K.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Neoleukin-2 enhances anti-tumour immunity downstream of peptide vaccination targeted by and anti-MHC class II VHH]]></article-title>
<source><![CDATA[Open Biology]]></source>
<year>2020</year>
<volume>10</volume>
<numero>2</numero>
<issue>2</issue>
</nlm-citation>
</ref>
<ref id="B7">
<label>7</label><nlm-citation citation-type="book">
<source><![CDATA[Biological Buffer]]></source>
<year></year>
<publisher-name><![CDATA[PanReac &amp; AppliChem]]></publisher-name>
</nlm-citation>
</ref>
<ref id="B8">
<label>8</label><nlm-citation citation-type="book">
<source><![CDATA[Buffer Reference Center]]></source>
<year></year>
<publisher-name><![CDATA[MERCK]]></publisher-name>
</nlm-citation>
</ref>
<ref id="B9">
<label>9</label><nlm-citation citation-type="book">
<person-group person-group-type="author">
<name>
<surname><![CDATA[MOHAN]]></surname>
<given-names><![CDATA[C.]]></given-names>
</name>
</person-group>
<source><![CDATA[Buffers: A guide for the preparation and use of buffers in biological systems]]></source>
<year>2006</year>
<edition>3rd</edition>
<page-range>30</page-range><publisher-name><![CDATA[EDM Bioscience]]></publisher-name>
</nlm-citation>
</ref>
<ref id="B10">
<label>10</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[ZBACNIK]]></surname>
<given-names><![CDATA[R.]]></given-names>
</name>
<name>
<surname><![CDATA[HOLCOMB]]></surname>
<given-names><![CDATA[D.]]></given-names>
</name>
<name>
<surname><![CDATA[KATAYAMA]]></surname>
<given-names><![CDATA[D.]]></given-names>
</name>
<name>
<surname><![CDATA[MURPHY]]></surname>
<given-names><![CDATA[B.]]></given-names>
</name>
<name>
<surname><![CDATA[PAYNE]]></surname>
<given-names><![CDATA[R.]]></given-names>
</name>
<name>
<surname><![CDATA[COCCARO]]></surname>
<given-names><![CDATA[R.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Role of buffers in protein formulations]]></article-title>
<source><![CDATA[Journal of Pharmaceutical Sciences]]></source>
<year>2017</year>
<volume>106</volume>
<numero>3</numero>
<issue>3</issue>
<page-range>713-33</page-range></nlm-citation>
</ref>
<ref id="B11">
<label>11</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[RAMÒN-SIERRA]]></surname>
<given-names><![CDATA[J.]]></given-names>
</name>
<name>
<surname><![CDATA[RUIZ-RUIZ]]></surname>
<given-names><![CDATA[J.]]></given-names>
</name>
<name>
<surname><![CDATA[ORTIZ-VÀZQUEZ]]></surname>
<given-names><![CDATA[E.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Electrophoresis characterisation of protein as a method to establish the entomological origin of stingless bee honeys]]></article-title>
<source><![CDATA[Food Chemistry]]></source>
<year>2015</year>
<volume>183</volume>
<page-range>43-8</page-range></nlm-citation>
</ref>
<ref id="B12">
<label>12</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[SHARMA]]></surname>
<given-names><![CDATA[S.]]></given-names>
</name>
<name>
<surname><![CDATA[AGARWAL]]></surname>
<given-names><![CDATA[G.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Interactions of proteins with immobilized metal ions role of ionic strength and pH]]></article-title>
<source><![CDATA[Journal of Colloid and Interface Science]]></source>
<year>2001</year>
<volume>243</volume>
<page-range>261-73</page-range></nlm-citation>
</ref>
<ref id="B13">
<label>13</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[CHEUNG]]></surname>
<given-names><![CDATA[R.]]></given-names>
</name>
<name>
<surname><![CDATA[WONG]]></surname>
<given-names><![CDATA[J.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Immobilized metal ion affinity chromatography: a review on its applications]]></article-title>
<source><![CDATA[Applied Microbiology and Biotechnology]]></source>
<year>2012</year>
<volume>96</volume>
<page-range>1411-20</page-range></nlm-citation>
</ref>
<ref id="B14">
<label>14</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[WANG]]></surname>
<given-names><![CDATA[W.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Protein aggregation and its inhibition in biopharmaceutics]]></article-title>
<source><![CDATA[International Journal of Pharmaceutics]]></source>
<year>2005</year>
<volume>289</volume>
<page-range>1-30</page-range></nlm-citation>
</ref>
<ref id="B15">
<label>15</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[BUTZ]]></surname>
<given-names><![CDATA[M.]]></given-names>
</name>
<name>
<surname><![CDATA[DEVENISH]]></surname>
<given-names><![CDATA[S.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Interleukin-2 stability in changing buffer and temperature conditions]]></article-title>
<source><![CDATA[Fluidic Analytics]]></source>
<year>2018</year>
</nlm-citation>
</ref>
<ref id="B16">
<label>16</label><nlm-citation citation-type="book">
<person-group person-group-type="author">
<name>
<surname><![CDATA[DE LA VARA]]></surname>
<given-names><![CDATA[R.]]></given-names>
</name>
<name>
<surname><![CDATA[GUTIÈRREZ]]></surname>
<given-names><![CDATA[H.]]></given-names>
</name>
</person-group>
<source><![CDATA[Análisis y diseño de experimentos]]></source>
<year>2012</year>
<edition>2nd</edition>
<page-range>545</page-range><publisher-name><![CDATA[McGraw-Hill]]></publisher-name>
</nlm-citation>
</ref>
<ref id="B17">
<label>17</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[AMSTRONG]]></surname>
<given-names><![CDATA[J.]]></given-names>
</name>
<name>
<surname><![CDATA[WENBY]]></surname>
<given-names><![CDATA[J.]]></given-names>
</name>
<name>
<surname><![CDATA[MEISELMAN]]></surname>
<given-names><![CDATA[H.]]></given-names>
</name>
<name>
<surname><![CDATA[FISHER]]></surname>
<given-names><![CDATA[T.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[The hydrodynamic radii of macromolecules and their effect on red blood cell aggregation]]></article-title>
<source><![CDATA[Biophysical Journal]]></source>
<year>2004</year>
<volume>87</volume>
<page-range>4259-70</page-range></nlm-citation>
</ref>
<ref id="B18">
<label>18</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[MASON]]></surname>
<given-names><![CDATA[B.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Liquid-liquid Phase Separation of Monoclonal Antibody and Nonmonotonic Influence of Hofmeister Anions]]></article-title>
<person-group person-group-type="editor">
<name>
<surname><![CDATA[ZHANG-VAN]]></surname>
<given-names><![CDATA[J.]]></given-names>
</name>
<name>
<surname><![CDATA[ZHANG]]></surname>
<given-names><![CDATA[L.]]></given-names>
</name>
<name>
<surname><![CDATA[REMMELE]]></surname>
<given-names><![CDATA[R.]]></given-names>
</name>
<name>
<surname><![CDATA[ZHANG]]></surname>
<given-names><![CDATA[J.]]></given-names>
</name>
</person-group>
<source><![CDATA[Biophysical Journal]]></source>
<year>2010</year>
<volume>99</volume>
<numero>11</numero>
<issue>11</issue>
<page-range>3792-800</page-range></nlm-citation>
</ref>
</ref-list>
</back>
</article>
